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Cited by 124Epigenetics and DNA MethylationGenomics and Chromatin DynamicsGenetics and Neurodevelopmental Disorders

A genome-wide screen for modifiers of transgene variegation identifies genes with critical roles in development

Open access
Ashe, Alyson, Morgan, Daniel K, Whitelaw, Nadia C, Bruxner, Timothy J, Vickaryous, Nicola K, Cox, Liza L, Butterfield, Natalie C, Wicking, Carol +5 more·2008·Genome Biology
DOI 10.1186/gb-2008-9-12-r182PMC PMC2646286
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Abstract

Background: Some years ago we established an N-ethyl-N-nitrosourea screen for modifiers of transgene variegation in the mouse and a preliminary description of the first six mutant lines, named MommeD1-D6, has been published. We have reported the underlying genes in three cases: MommeD1 is a mutation in SMC hinge domain containing 1 (Smchd1), a novel modifier of epigenetic gene silencing; MommeD2 is a mutation in DNA methyltransferase 1 (Dnmt1); and MommeD4 is a mutation in Smarca 5 (Snf2h), a known chromatin remodeler. The identification of Dnmt1 and Smarca5 attest to the effectiveness of the screen design. Results: We have now extended the screen and have identified four new modifiers, MommeD7-D10. Here we show that all ten MommeD s link to unique sites in the genome, that homozygosity for the mutations is associated with severe developmental abnormalities and that heterozygosity results in phenotypic abnormalities and reduced reproductive fitness in some cases. In addition, we have now identified the underlying genes for MommeD5 and MommeD10. MommeD5 is a mutation in Hdac1, which encodes histone deacetylase 1, and MommeD10 is a mutation in Baz1b (also known as Williams syndrome transcription factor), which encodes a transcription factor containing a PHD-type zinc finger and a bromodomain. We show that reduction in the level of Baz1b in the mouse results in craniofacial features reminiscent of Williams syndrome. Conclusions: These results demonstrate the importance of dosage-dependent epigenetic reprogramming in the development of the embryo and the power of the screen to provide mouse models to study this process.

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Written from the paper’s full text.

TL;DR

An extended ENU screen in mice identified four new modifiers of GFP transgene variegation, MommeD7–D10, all semidominant and associated with homozygous embryonic or perinatal lethality. The study mapped the mutations, identified Hdac1 (MommeD5) and Baz1b (MommeD10) as causative genes, and linked reduced Baz1b to craniofacial features resembling Williams-Beuren syndrome.

Key findings

  • Screening an additional 400 G1 offspring recovered MommeD7–D10, bringing the total to 1,000 G1 offspring screened. MommeD7 is a suppressor of variegation (heterozygotes: 80 ± 3% GFP-expressing erythrocytes vs wild-type 55 ± 7%, p ≤ 0.0001), while MommeD8, D9 and D10 are enhancers (e.g., MommeD8 heterozygotes 41 ± 4%, homozygotes 15 ± 4%; MommeD10 heterozygotes 44 ± 3%, homozygotes 22 ± 2%; p ≤ 0.0001).
  • All ten MommeDs behave semidominantly, and homozygosity is associated with embryonic or perinatal lethality. Timing varied: MommeD5, D6 and D9 homozygotes arrested around 8–9 dpc; MommeD3 by or before 14.5 dpc; MommeD7 homozygotes died in the first few days after birth; most MommeD8 and MommeD10 homozygotes died between P1 and P21.
  • MommeD5 carries a 7 bp deletion in exon 13 of Hdac1, and MommeD10 carries a T→G transversion in exon 7 of Baz1b causing L733R and reduced Baz1b protein. MommeD10 homozygotes were smaller and had craniofacial anomalies reminiscent of Williams-Beuren syndrome, with some features also in heterozygotes.
  • DNA methylation at the transgene HS-40 enhancer was not significantly altered in MommeD5-/+ or MommeD10-/+ and MommeD10-/- mice compared with wild-type, suggesting these modifiers act through chromatin state rather than DNA methylation at this element.

Methods

  • ENU mutagenesis was performed in an FVB/NJ transgenic line expressing GFP in a variegated manner in erythrocytes; 1,000 G1 offspring were screened at 3 weeks of age, and heritable mutations were confirmed over at least 5 generations using at least 30 litters.
  • GFP expression was measured by flow cytometry with a positive gate set to exclude 99.9% of wild-type erythrocytes; mutants were mapped by linkage analysis using FVB/C57 backcrosses or F2 intercrosses, followed by candidate gene sequencing.
  • Supporting analyses included western blotting, quantitative RT-PCR, bisulfite sequencing of the transgene HS-40 enhancer, reticulocyte staining/FACS, micro-computed tomography of skulls, and whole-mount in situ hybridization for Baz1b expression.

Limitations

  • Stated: extensive phenotyping of heterozygous MommeD lines was not carried out, although heterozygous effects such as haematopoietic abnormalities in MommeD7-/+ and litter size reductions in MommeD9/D10 were noted.
  • Stated/evident: the underlying genes were identified in only five of ten MommeDs; several mapped intervals still contained many genes (e.g., MommeD3 123 genes, MommeD6 32, MommeD8 54, MommeD9 80), so causality was not established for those lines.
  • Evident: the GC-rich transgene promoter could not be analyzed by bisulfite sequencing because the cloned converted fragment was refractory to bacterial growth, so methylation analysis was limited to the HS-40 enhancer; some lethality timing relied on abnormal/resorbed embryos and limited genotyping.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1186/gb-2008-9-12-r182

Cites

48 of 48 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 57 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    The GFP transgene integrated into chromosome 1 at 47,747,486 bp (UCSC July 2007 assembly).

    “PCR using primers specific to the 3' end of the transgene construct in combination with degenerate random tagging primers (genome walking) revealed that the transgene had integrated into chromosome 1 at 47,747,486 bp (UCSC web browser, July 2007 assembly).”
    Quote in the paperNot a substantial claim
  • Findingown data

    An extended ENU screen for modifiers of transgene variegation identified four new modifiers, MommeD7-D10.

    “An extended ENU screen for modifiers of transgene variegation identified four new modifiers, MommeD7-D10.”
    Quote in the paperSubstantial claim
  • Findingown data

    Sequencing revealed a 7 bp deletion (GAAGCCA) in exon 13 of Hdac1 in MommeD5 mutants.

    “Sequencing of all exons, including exon/intron boundaries, from two heterozygous and two wild-type individuals revealed a 7 bp deletion (GAAGCCA) in exon 13 in the mutants (Figure 5a).”
    Quote in the paperSubstantial claim
  • Findingown data

    Each of the ten MommeD mutations maps to a unique region of the genome.

    “These data show that each of the ten MommeD mutations maps to a unique region of the genome.”
    Quote in the paperSubstantial claim
  • Findingown data

    MommeD8 homozygotes were significantly smaller than their wild-type and heterozygous littermates.

    “MommeD8 homozygotes were significantly smaller (6.60 g ± 0.25 standard error of the mean (SEM)) than their wild-type (8.54 g ± 0.33 SEM, p < 0.001) and heterozygous (8.65 g ± 0.29 SEM, p < 0.0001) littermates.”
    Quote in the paperSubstantial claim
  • May combine two claims. 49
  • The quote only partly states this claim. 1
  • Classified as probably not a substantial claim. 24

  • May combine two claims.

    Findingown data

    The transgene integration site does not disrupt any annotated genes and is approximately 1 Mb from the closest annotated transcript.

    “The integration site does not disrupt any annotated genes, and is approximately 1 Mb from the closest annotated transcript.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    An antibody recognizing the Hdac1 carboxyl terminus showed 50% reduction of binding in MommeD5-/+ embryos and negligible binding in MommeD5-/- embryos.

    “An antibody that recognizes the carboxyl terminus of Hdac1 showed a 50% reduction of binding in 10.5 dpc MommeD5-/+ embryos, and negligible binding in MommeD5-/- embryos (Figure 5b), confirming that this region of the protein has been altered in the MommeD5 line.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Adult heterozygous MommeD7 individuals have severe splenomegaly and a marked increase in reticulocytes in peripheral blood.

    “Further analysis of adult heterozygous individuals revealed severe splenomegaly (Figure 3b) and a marked increase in reticulocytes in peripheral blood (Figure 3c).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    MommeD8, D9 and D10 are enhancers of variegation; the percentages of expressing cells were significantly lower than in wild-type individuals.

    “MommeD8, D9 and D10 are enhancers of variegation, that is, the percentages of expressing cells were significantly lower than they were in wild-type individuals (Table 1).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In MommeD10, death of homozygotes occurred after birth, and preliminary data at P7 indicated death in the first week of life.

    “In the case of MommeD10 the data suggest that death of homozygotes occurred after birth (Table 3), and preliminary data collected at P7 indicated death in the first week of life (data not shown).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The Hdac1 deletion alters the reading frame, changing the last 12 amino acids and adding 25 extra amino acids.

    “This deletion alters the reading frame, changing the last 12 amino acids and adding 25 extra amino acids.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Each mutant line has a significantly different expression profile from wild-type littermates, reproducible over many generations.

    “Each mutant line has a significantly different expression profile to that of wild-type littermates, reproducible over many generations.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    For MommeD9 and MommeD10, the litter size reduction was associated with a deviation from Mendelian patterns of inheritance and a reduction in the number of mutants.

    “A breakdown of the offspring by sex and genotype revealed that for MommeD9 and MommeD10, the litter size reduction was associated with a deviation from Mendelian patterns of inheritance (p < 0.05 in both cases) and a reduction in the number of mutants (Figure 4).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Some MommeD8-/- mice were viable at weaning but they were rare.

    “Some MommeD8-/- mice (classified by their GFP expression profile and progeny testing) were viable at weaning but they were rare (Figure 1, Table 2).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Homozygous MommeD7 mutants were never seen at weaning, and preliminary observations suggest they die in the first few days after birth.

    “Homozygous MommeD7 mutants were never seen at weaning (Table 2), and preliminary observations suggest that they die in the first few days after birth.”
    Quote in the paperSubstantial claim

  • The quote only partly states this claim.

    Findingown data

    The mean fluorescence level in expressing cells also changed in the MommeD mutants.

    “The mean fluorescence level in expressing cells also changed.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Findingown data

    There is a suggestion of some heterozygous death in MommeD8 and, to a lesser extent, MommeD10, but this is not statistically significant.

    “There is also a suggestion of some heterozygous death in the case of MommeD8 and, to a lesser extent, MommeD10 but this is not statistically significant.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    MommeD7-/+ mice had a threefold increase in the percentage of reticulocytes compared to MommeD7+/+ mice, and GFP fluorescence was higher in reticulocytes than mature red cells in both genotypes.

    “As expected, MommeD7-/+ mice had a threefold increase in the percentage of reticulocytes compared to MommeD7+/+ mice (Figure 3d), and the percentage of GFP fluorescence in both MommeD7-/+ and MommeD7+/+ was higher in reticulocytes than mature red cells (Figure 3e).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    MommeD7 is a suppressor of variegation; the percentage of cells expressing the transgene was significantly higher than in wild-type individuals.

    “MommeD7 is a suppressor of variegation, that is, the percentage of cells expressing the transgene was significantly higher than it was in wild-type individuals (Table 1).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Some MommeD10-/- individuals survived to weaning but they were extremely rare.

    “Some MommeD10-/- individuals survived to weaning but they were extremely rare.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingcitation

    The frequency of finding these mutations was 1 in 100 G1 offspring, similar to previous results.

    “The frequency with which we found these mutations, 1 in 100 G1 offspring, was similar to our previous results [10].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [10] Blewitt ME, Vickaryous NK, Hemley SJ, Ashe A, Bruxner TJ, Preis JI, Arkell R, Whitelaw E: An N-ethyl-N-nitrosourea screen for genes involved in variegation in the mouse. Proc Natl Acad Sci USA. 2005, 102: 7629-7634. 10.1073/pnas.0409375102. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    The MommeD7 mapping region contains 10 genes.

    “This region contains 10 genes.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Following crosses between heterozygous males and wild-type females in the FVB strain, significant litter size reductions were found in MommeD9 and MommeD10, but not in MommeD7 and MommeD8.

    “Following crosses between heterozygous males and wild-type females in the FVB strain, we found significant litter size reductions in the cases of MommeD9 and MommeD10, but not in the cases of MommeD7 and MommeD8.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    From 9.5 dpc expression is evident in the somites and in the forelimb bud as it emerges from the lateral plate mesoderm.

    “From 9.5 dpc expression is evident in the somites and in the forelimb bud as it emerges from the lateral plate mesoderm (Figure 9b).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    In the facial primordia, Baz1b is expressed in branchial arch 1 as it first emerges, and continues later in development in both the maxillary and mandibular components of branchial arch 1 and branchial arch 2.

    “In the facial primordia, Baz1b is expressed in branchial arch 1 as it first emerges (Figure 9g), and continues later in development in both the maxillary and mandibular components of branchial arch 1 and branchial arch 2 (Figure 9c-e, h, i).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Western blot analysis showed reduced levels of Baz1b protein in embryonic and adult MommeD10-/- tissue, with MommeD10-/+ tissue showing intermediate levels.

    “Western blot analysis showed reduced levels of Baz1b protein in both embryonic and adult MommeD10-/- tissue, with MommeD10-/+ tissue showing intermediate levels (Figure 6c and data not shown), suggesting that the mutant protein is much less stable than its wild-type counterpart.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    Diffuse mesenchymal expression in both the forelimb and hindlimb continues until 12.5 dpc when it is restricted to the interdigital mesenchyme.

    “Diffuse mesenchymal expression in both the forelimb and hindlimb continues until 12.5 dpc when it is restricted to the interdigital mesenchyme (data not shown).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Homozygote skulls were significantly different from wild type in length:height, width:height, and length:width ratios.

    “Homozygote skulls were significantly different to wild type (Student's t-test, length:height ratio, p < 0.01; width:height ratio, p < 0.01; length:width ratio, p < 0.05)”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Visual inspection of three-dimensional reconstructions confirmed that homozygote skulls were more bulbous and showed flattening of the nasal bone and upward curvature of the nasal tip.

    “Visual inspection of the three-dimensional reconstructions confirmed the original observation that homozygote's skulls were more bulbous and showed a flattening of the nasal bone and upward curvature of the nasal tip (Figure 8c).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Dnmt3b+/- mice showed increased GFP transgene expression and decreased CpG methylation at the HS-40 element compared to wild-type C57BL/6J mice.

    “Mice heterozygous for a null allele of Dnmt3b, which showed an increase in expression of the GFP transgene from 37 ± 3% in the wild-type mice to 55.5 ± 2.5% in the Dnmt3b+/- mice (in both cases mice were hemizygous for the transgene; see Materials and methods), showed a decrease in CpG methylation at the HS-40 element (31%; Figure 7b) compared to that seen in the wild-type C57BL/6J mouse strain (6”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Expression in the branchial arches is primarily mesenchymal, and is enriched in the rostral distal margin of the mandible, and the caudal distal margin of branchial arch 2.

    “Expression in the branchial arches is primarily mesenchymal, and is enriched in the rostral distal margin of the mandible, and the caudal distal margin of branchial arch 2 (Figure 9c-e, h).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    We checked the sequence and expression of Gtf2ird1 in MommeD10 mutants and found no abnormalities.

    “We checked the sequence and expression of Gtf2ird1 in MommeD10 mutants and found no abnormalities (data not shown).”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingnone given

    The AciI site is created by the MommeD10 point mutation.

    “The AciI site is created by the MommeD10 point mutation.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    We have now identified the underlying genes in five of the ten cases, two of which, Hdac1 and Baz1b, we report here.

    “We have now identified the underlying genes in five of the ten cases, two of which, Hdac1 and Baz1b, we report here.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Findingnone given

    At least half of the MommeDs are important during gastrulation.

    “It is interesting that at least half of the MommeDs are important during gastrulation.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingcitation

    Extension of the screen has produced four new MommeDs, MommeD7-D10, all of which behave in a semidominant fashion, as do the six previously reported.

    “Extension of the screen has produced four new MommeDs, MommeD7-D10, all of which behave in a semidominant fashion, as do the six previously reported [10].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [10] Blewitt ME, Vickaryous NK, Hemley SJ, Ashe A, Bruxner TJ, Preis JI, Arkell R, Whitelaw E: An N-ethyl-N-nitrosourea screen for genes involved in variegation in the mouse. Proc Natl Acad Sci USA. 2005, 102: 7629-7634. 10.1073/pnas.0409375102. source

      Not checked in the free run.

  • May combine two claims.

    Findingnone given

    A total of 1,000 G1 offspring were screened at 3 weeks of age, from which ten heritable dominant mutations were identified.

    “A total of 1,000 G1 offspring were screened at 3 weeks of age, from which ten heritable dominant mutations were identified.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    MommeD2 is a mutation in Dnmt1, encoding a DNA methyltransferase, and MommeD4 is a mutation in Smarca5, encoding Snf2h, a chromatin-remodeling enzyme.

    “MommeD2 is a mutation in DNA methyltransferase 1, Dnmt1, encoding a DNA methyltransferase, and MommeD4 is a mutation in Smarca5, encoding Snf2h, a chromatin-remodeling enzyme [12].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [12] Chong S, Vickaryous N, Ashe A, Zamudio N, Youngson N, Hemley S, Stopka T, Skoultchi A, Matthews J, Scott HS, de Kretser D, O'Bryan M, Blewitt M, Whitelaw E: Modifiers of epigenetic reprogramming show paternal effects in the mouse. Nat Genet. 2007, 39: 614-622. 10.1038/ng2031. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    MommeD1 is a mutation in SmcHD1, encoding a previously uncharacterized protein containing an SMC protein domain, and this protein has a critical role in X inactivation.

    “MommeD1 is a mutation in SMC hinge domain containing 1 (SmcHD1), encoding a previously uncharacterized protein containing a domain normally found in SMC proteins and we have gone on to show that this protein has a critical role in X inactivation [11].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [11] Blewitt ME, Gendrel AV, Pang Z, Sparrow DB, Whitelaw N, Craig JM, Apedaile A, Hilton DJ, Dunwoodie SL, Brockdorff N, Kay GF, Whitelaw E: SmcHD1, containing a structural-maintenance-of-chromosomes hinge domain, has a critical role in X inactivation. Nat Genet. 2008, 40: 663-669. 10.1038/ng.142. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    All six previously reported Momme mutations were dosage-effect genes, and five of the six were homozygous lethal with loss of homozygotes apparent at weaning.

    “We reported that all six were dosage-effect genes and five of the six were homozygous lethal, with loss of homozygotes apparent at weaning, but no knowledge of when death occurred.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [10] Blewitt ME, Vickaryous NK, Hemley SJ, Ashe A, Bruxner TJ, Preis JI, Arkell R, Whitelaw E: An N-ethyl-N-nitrosourea screen for genes involved in variegation in the mouse. Proc Natl Acad Sci USA. 2005, 102: 7629-7634. 10.1073/pnas.0409375102. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Approximately one-third of the Drosophila modifier genes have been identified, and most play critical roles in epigenetic gene silencing.

    “Approximately one-third of these have been identified and, as expected, most turn out to play critical roles in epigenetic gene silencing [1,9].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [1] Henikoff S: Position-effect variegation after 60 years. Trends Genet. 1990, 6: 422-426. 10.1016/0168-9525(90)90304-O. source

      Not checked in the free run.

    • cites [9] Dorn R, Krauss V, Reuter G, Saumweber H: The enhancer of position-effect variegation of Drosophila, E(var)3-93D, codes for a chromatin protein containing a conserved domain common to several transcriptional regulators. Proc Natl Acad Sci USA. 1993, 90: 11376-11380. 10.1073/pnas.90.23.11376. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Identified Drosophila modifier genes include genes encoding proteins involved in heterochromatin formation, such as HP1 and histone methyltransferases.

    “These include genes encoding proteins involved in heterochromatin formation, for example, HP1 and histone methyltransferases [8].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [8] Schotta G, Ebert A, Dorn R, Reuter G: Position-effect variegation and the genetic dissection of chromatin regulation in Drosophila. Semin Cell Dev Biol. 2003, 14: 67-75. 10.1016/S1084-9521(02)00138-6. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    A preliminary description of the first six heritable Momme mutations, following screening of 608 G1 offspring, has been published.

    “A preliminary description of the first six heritable mutations, which we refer to as Modifiers of murine metastable epialleles or Mommes, following the screening of 608 G1 offspring, has been published [10].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [10] Blewitt ME, Vickaryous NK, Hemley SJ, Ashe A, Bruxner TJ, Preis JI, Arkell R, Whitelaw E: An N-ethyl-N-nitrosourea screen for genes involved in variegation in the mouse. Proc Natl Acad Sci USA. 2005, 102: 7629-7634. 10.1073/pnas.0409375102. source

      Not checked in the free run.

  • May combine two claims.

    Premisenone given

    The extent of variegation at the wv locus is sensitive to strain background, suggesting the existence of genetic modifiers.

    “The extent of the variegation at the wv locus, that is, the ratio of red to white patches in the eye, was known to be sensitive to strain background, suggesting the existence of genetic modifiers.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    The best characterized example of variegation in mammals is the coat color of mice carrying the Avy allele.

    “The best characterized example of variegation in mammals is the coat color of mice carrying the Avy allele [3,4].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [3] Wolff GL: Influence of maternal phenotype on metabolic differentiation of agouti locus mutants in the mouse. Genetics. 1978, 88: 529-539. source

      Not checked in the free run.

    • cites [4] Rakyan VK, Blewitt ME, Druker R, Preis JI, Whitelaw E: Metastable epialleles in mammals. Trends Genet. 2002, 18: 348-351. 10.1016/S0168-9525(02)02709-9. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    In mice carrying the Avy allele, there is a correlation between DNA methylation at the promoter and silencing of the gene.

    “In this case there is a correlation between DNA methylation at the promoter and silencing of the gene [5,6].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [5] Waterland RA, Jirtle RL: Transposable elements: targets for early nutritional effects on epigenetic gene regulation. Mol Cell Biol. 2003, 23: 5293-5300. 10.1128/MCB.23.15.5293-5300.2003. source

      Not checked in the free run.

    • cites [6] Morgan HD, Sutherland HG, Martin DI, Whitelaw E: Epigenetic inheritance at the agouti locus in the mouse. Nat Genet. 1999, 23: 314-318. 10.1038/15490. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Drosophila modifier screens suggest there are between 100 and 150 genes that modify position effect variegation.

    “These screens have been continued to saturation and the results suggest that there are between 100 and 150 such genes [7,8].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [7] Reuter G, Spierer P: Position effect variegation and chromatin proteins. Bioessays. 1992, 14: 605-612. 10.1002/bies.950140907. source

      Not checked in the free run.

    • cites [8] Schotta G, Ebert A, Dorn R, Reuter G: Position-effect variegation and the genetic dissection of chromatin regulation in Drosophila. Semin Cell Dev Biol. 2003, 14: 67-75. 10.1016/S1084-9521(02)00138-6. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Interpretationreasoning

    Because the mice are homozygous for the GFP transgene, the increase in mean fluorescence is mainly due to an increase in the proportion of expressing cells with two active GFP alleles.

    “We presume that since the mice are homozygous for the GFP transgene, this is mainly due to an increase in the proportion of expressing cells with two active GFP alleles.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    In MommeD8, D9 and D10, the mean fluorescence levels were slightly lower than in wild-type littermates, consistent with a presumed reduction in the proportion of cells with two active GFP alleles.

    “In the cases of MommeD8, D9 and D10 the mean fluorescence levels were slightly lower than that seen in the wild-type littermates, consistent with a presumed reduction in the proportion of cells with two active GFP alleles.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    MommeD1 is homozygous lethal in females only, with death occurring around mid-gestation.

    “MommeD1 is homozygous lethal in females only, with death occurring around mid-gestation [10,11].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [10] Blewitt ME, Vickaryous NK, Hemley SJ, Ashe A, Bruxner TJ, Preis JI, Arkell R, Whitelaw E: An N-ethyl-N-nitrosourea screen for genes involved in variegation in the mouse. Proc Natl Acad Sci USA. 2005, 102: 7629-7634. 10.1073/pnas.0409375102. source

      Not checked in the free run.

    • cites [11] Blewitt ME, Gendrel AV, Pang Z, Sparrow DB, Whitelaw N, Craig JM, Apedaile A, Hilton DJ, Dunwoodie SL, Brockdorff N, Kay GF, Whitelaw E: SmcHD1, containing a structural-maintenance-of-chromosomes hinge domain, has a critical role in X inactivation. Nat Genet. 2008, 40: 663-669. 10.1038/ng.142. source

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    During breeding of each mutant line, the expression profiles remained constant, consistent with following a single mutation in each case.

    “During the breeding of each mutant line, the expression profiles remained constant, consistent with the idea that we were following a single mutation in each case.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    Litter size at birth was not significantly different from wild-type litters, suggesting that death of most MommeD8-/- individuals occurred after birth and before weaning.

    “Litter size at birth was not significantly different from that seen in wild-type litters (data not shown), suggesting that the death of most MommeD8-/- individuals occurred after birth and before weaning.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    The transgene integration site is neither centromeric nor telomeric, so the silencing is presumably related to the multicopy nature of the transgene array.

    “This site of integration is neither centromeric nor telomeric, and so presumably the silencing is related to the multicopy nature of the transgene array [13,14].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [13] Garrick D, Fiering S, Martin DI, Whitelaw E: Repeat-induced gene silencing in mammals. Nat Genet. 1998, 18: 56-59. 10.1038/ng0198-56. source

      Not checked in the free run.

    • cites [14] Preis JI, Downes M, Oates NA, Rasko JE, Whitelaw E: Sensitive flow cytometric analysis reveals a novel type of parent-of-origin effect in the mouse genome. Curr Biol. 2003, 13: 955-959. 10.1016/S0960-9822(03)00335-X. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    MommeD2 and MommeD4 are homozygous lethal at 8.5 days post-coitus and 17.5 days post-coitus, respectively.

    “MommeD2 and MommeD4 are homozygous lethal at 8.5 days post-coitus (dpc) and 17.5 dpc, respectively [10,12].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [10] Blewitt ME, Vickaryous NK, Hemley SJ, Ashe A, Bruxner TJ, Preis JI, Arkell R, Whitelaw E: An N-ethyl-N-nitrosourea screen for genes involved in variegation in the mouse. Proc Natl Acad Sci USA. 2005, 102: 7629-7634. 10.1073/pnas.0409375102. source

      Not checked in the free run.

    • cites [12] Chong S, Vickaryous N, Ashe A, Zamudio N, Youngson N, Hemley S, Stopka T, Skoultchi A, Matthews J, Scott HS, de Kretser D, O'Bryan M, Blewitt M, Whitelaw E: Modifiers of epigenetic reprogramming show paternal effects in the mouse. Nat Genet. 2007, 39: 614-622. 10.1038/ng2031. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Examples of paternal effects resulting from haploinsufficiency of modifiers of epigenetic gene silencing in the mouse have been published previously.

    “We have previously published examples of paternal effects resulting from haploinsufficiency of modifiers of epigenetic gene silencing in the mouse [12].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [12] Chong S, Vickaryous N, Ashe A, Zamudio N, Youngson N, Hemley S, Stopka T, Skoultchi A, Matthews J, Scott HS, de Kretser D, O'Bryan M, Blewitt M, Whitelaw E: Modifiers of epigenetic reprogramming show paternal effects in the mouse. Nat Genet. 2007, 39: 614-622. 10.1038/ng2031. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationown data

    There appears to be a skewed sex ratio in the wild-type offspring of MommeD9 sires, suggesting the phenotype of the father can affect his wild-type offspring.

    “There also appears to be a skewed sex ratio in the wild-type offspring of MommeD9 sires, suggesting the phenotype of the father can affect his wild-type offspring.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data

    In MommeD8 and MommeD10, fewer individuals with severe phenotypes were observed than predicted by Mendelian inheritance, suggesting reduced viability of homozygotes.

    “In both cases, fewer individuals with the severe phenotypes were observed than predicted by Mendelian inheritance, suggesting reduced viability of the homozygotes (Table 2).”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Premisecitation

    As the percentage of expressing cells increases, the mean fluorescence of the expressing cells increases.

    “We have reported previously that as the percentage of expressing cells increases, the mean fluorescence of the expressing cells increases [10].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [10] Blewitt ME, Vickaryous NK, Hemley SJ, Ashe A, Bruxner TJ, Preis JI, Arkell R, Whitelaw E: An N-ethyl-N-nitrosourea screen for genes involved in variegation in the mouse. Proc Natl Acad Sci USA. 2005, 102: 7629-7634. 10.1073/pnas.0409375102. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    A knockout of Hdac1 has been reported, and homozygous embryos died around 9.5 dpc.

    “A knockout of Hdac1 has been reported and the homozygous embryos died around 9.5 dpc [21], similar to the time of death observed in MommeD5-/- embryos (Figure 5c).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [21] Lagger G, O'Carroll D, Rembold M, Khier H, Tischler J, Weitzer G, Schuettengruber B, Hauser C, Brunmeir R, Jenuwein T, Seiser C: Essential function of histone deacetylase 1 in proliferation control and CDK inhibitor repression. EMBO J. 2002, 21: 2672-2681. 10.1093/emboj/21.11.2672. source

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    In MommeD8 and MommeD10, three expression profiles were observed, suggesting viability of some homozygotes; in MommeD10 this was later confirmed by genotyping for the point mutation.

    “In the cases of MommeD8 and MommeD10, three expression profiles were observed, suggesting viability of some homozygotes (Figure 1, Tables 1 and 2) and in the case of MommeD10 this was later confirmed by genotyping for the point mutation.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    At 17.5 dpc, approximately one-quarter of the embryos were pale, suggesting a red cell defect in MommeD7 homozygotes.

    “At 17.5 dpc, approximately one-quarter of the embryos were pale (Table 3, Figure 3a), suggesting a red cell defect in the homozygotes.”
    Quote in the paperSubstantial claim
    • The authors state this as an assumption: Abnormal pale embryos at 17.5 dpc from MommeD7 intercrosses are homozygous for MommeD7.

  • May combine two claims.

    Interpretationcitation

    Overall, the skull shape in mutant animals is reminiscent of the head shape seen in WBS, including a small upturned nose with flat nasal bridge, micrognathia (or mandibular hypoplasia), malocclusion, bi-temporal narrowing and prominent forehead.

    “Overall, the skull shape in mutant animals is reminiscent of the head shape seen in WBS, including a small upturned nose with flat nasal bridge, micrognathia (or mandibular hypoplasia), malocclusion, bi-temporal narrowing and prominent forehead [34].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [34] Perez Jurado AL: Williams-Beuren syndrome: a model of recurrent genomic mutation. Horm Res. 2003, 59 (Suppl 1): 106-113. 10.1159/000067836. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Baz1b is expressed in the mouse embryo from around 9.5 dpc and at 11.5 dpc in limb buds, tail and brain.

    “It has previously been shown that Baz1b is expressed in the mouse embryo from around 9.5 dpc and whole mount in situ at 11.5 dpc showed expression in limb buds, tail and brain [24].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [24] Kitagawa H, Fujiki R, Yoshimura K, Mezaki Y, Uematsu Y, Matsui D, Ogawa S, Unno K, Okubo M, Tokita A, Nakagawa T, Ito T, Ishimi Y, Nagasawa H, Matsumoto T, Yanagisawa J, Kato S: The chromatin-remodeling complex WINAC targets a nuclear receptor to promoters and is impaired in Williams syndrome. Cell. 2003, 113: 905-917. 10.1016/S0092-8674(03)00436-7. source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    Baz1b was chosen as the best candidate for MommeD10 because it contains a bromodomain and has been shown to form chromatin remodeling complexes and associate with replication foci and promoters.

    “The linked interval for MommeD10 contains 52 genes and Baz1b was chosen as the best candidate because it contains a bromodomain (a domain commonly associated with chromatin remodelers) and has recently been shown to form at least two chromatin remodeling complexes and associate with replication foci and promoters [23-25].”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [23] Bozhenok L, Wade PA, Varga-Weisz P: WSTF-ISWI chromatin remodeling complex targets heterochromatic replication foci. EMBO J. 2002, 21: 2231-2241. 10.1093/emboj/21.9.2231. source

      Not checked in the free run.

    • cites [24] Kitagawa H, Fujiki R, Yoshimura K, Mezaki Y, Uematsu Y, Matsui D, Ogawa S, Unno K, Okubo M, Tokita A, Nakagawa T, Ito T, Ishimi Y, Nagasawa H, Matsumoto T, Yanagisawa J, Kato S: The chromatin-remodeling complex WINAC targets a nuclear receptor to promoters and is impaired in Williams syndrome. Cell. 2003, 113: 905-917. 10.1016/S0092-8674(03)00436-7. source

      Not checked in the free run.

    • cites [25] Percipalle P, Fomproix N, Cavellan E, Voit R, Reimer G, Kruger T, Thyberg J, Scheer U, Grummt I, Farrants AK: The chromatin remodelling complex WSTF-SNF2h interacts with nuclear myosin 1 and has a role in RNA polymerase I transcription. EMBO Rep. 2006, 7: 525-530. source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Modifiers identified in this screen include DNA methyltransferases, chromatin remodelers and genes involved in histone modification, all of which have wide-ranging effects in the genome, making it difficult to unravel direct and indirect effects at any particular locus.

    “Modifiers identified in this screen include DNA methyltransferases, chromatin remodelers and genes involved in histone modification, all of which have wide-ranging effects in the genome, making it difficult to unravel direct and indirect effects at any particular locus.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Both MommeD5 and MommeD10 genes encode proteins involved in histone modification and chromatin remodeling.

    “This is consistent with the fact that both genes encode proteins involved in histone modification and chromatin remodeling [21,23-25,30-33].”
    Quote in the paperSubstantial claim0 of 8 sources checked
    • cites [21] Lagger G, O'Carroll D, Rembold M, Khier H, Tischler J, Weitzer G, Schuettengruber B, Hauser C, Brunmeir R, Jenuwein T, Seiser C: Essential function of histone deacetylase 1 in proliferation control and CDK inhibitor repression. EMBO J. 2002, 21: 2672-2681. 10.1093/emboj/21.11.2672. source

      Not checked in the free run.

    • cites [23] Bozhenok L, Wade PA, Varga-Weisz P: WSTF-ISWI chromatin remodeling complex targets heterochromatic replication foci. EMBO J. 2002, 21: 2231-2241. 10.1093/emboj/21.9.2231. source

      Not checked in the free run.

    • cites [24] Kitagawa H, Fujiki R, Yoshimura K, Mezaki Y, Uematsu Y, Matsui D, Ogawa S, Unno K, Okubo M, Tokita A, Nakagawa T, Ito T, Ishimi Y, Nagasawa H, Matsumoto T, Yanagisawa J, Kato S: The chromatin-remodeling complex WINAC targets a nuclear receptor to promoters and is impaired in Williams syndrome. Cell. 2003, 113: 905-917. 10.1016/S0092-8674(03)00436-7. source

      Not checked in the free run.

    • cites [25] Percipalle P, Fomproix N, Cavellan E, Voit R, Reimer G, Kruger T, Thyberg J, Scheer U, Grummt I, Farrants AK: The chromatin remodelling complex WSTF-SNF2h interacts with nuclear myosin 1 and has a role in RNA polymerase I transcription. EMBO Rep. 2006, 7: 525-530. source

      Not checked in the free run.

    • cites [30] Ahringer J: NuRD and SIN3 histone deacetylase complexes in development. Trends Genet. 2000, 16: 351-356. 10.1016/S0168-9525(00)02066-7. source

      Not checked in the free run.

    • cites [31] Taunton J, Hassig CA, Schreiber SL: A mammalian histone deacetylase related to the yeast transcriptional regulator Rpd3p. Science. 1996, 272: 408-411. 10.1126/science.272.5260.408. source

      Not checked in the free run.

    • cites [32] Fujiki R, Kim MS, Sasaki Y, Yoshimura K, Kitagawa H, Kato S: Ligand-induced transrepression by VDR through association of WSTF with acetylated histones. EMBO J. 2005, 24: 3881-3894. 10.1038/sj.emboj.7600853. source

      Not checked in the free run.

    • cites [33] Poot RA, Bozhenok L, Berg van den DL, Hawkes N, Varga-Weisz PD: Chromatin remodeling by WSTF-ISWI at the replication site: opening a window of opportunity for epigenetic inheritance?. Cell Cycle. 2005, 4: 543-546. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    People with atypical deletions and varying degrees of craniofacial abnormalities implicate both proximal and distal ends of the deletion, suggesting that more than one gene is responsible.

    “People with atypical deletions, and varying degrees of craniofacial abnormalities, implicate both proximal and distal ends of the deletion, suggesting that more than one gene is responsible [36-41].”
    Quote in the paperNot a substantial claim0 of 6 sources checked
    • cites [36] Botta A, Novelli G, Mari A, Novelli A, Sabani M, Korenberg J, Osborne LR, Digilio MC, Giannotti A, Dallapiccola B: Detection of an atypical 7q11.23 deletion in Williams syndrome patients which does not include the STX1A and FZD3 genes. J Med Genet. 1999, 36: 478-480.

      Not checked in the free run.

    • cites [37] Duba HC, Doll A, Neyer M, Erdel M, Mann C, Hammerer I, Utermann G, Grzeschik KH: The elastin gene is disrupted in a family with a balanced translocation t(7;16)(q11.23;q13) associated with a variable expression of the Williams-Beuren syndrome. Eur J Hum Genet. 2002, 10: 351-361. 10.1038/sj.ejhg.5200812. source

      Not checked in the free run.

    • cites [38] Edelmann L, Prosnitz A, Pardo S, Bhatt J, Cohen N, Lauriat T, Ouchanov L, González PJ, Manghi ER, Bondy P, Esquivel M, Monge S, Delgado MF, Splendore A, Francke U, Burton BK, McInnes LA: An atypical deletion of the Williams-Beuren syndrome interval implicates genes associated with defective visuospatial processing and autism. J Med Genet. 2007, 44: 136-143. 10.1136/jmg.2006.044537. source

      Not checked in the free run.

    • cites [39] Hirota H, Matsuoka R, Chen XN, Salandanan LS, Lincoln A, Rose FE, Sunahara M, Osawa M, Bellugi U, Korenberg JR: Williams syndrome deficits in visual spatial processing linked to GTF2IRD1 and GTF2I on chromosome 7q11.23. Genet Med. 2003, 5: 311-321. source

      Not checked in the free run.

    • cites [40] Howald C, Merla G, Digilio MC, Amenta S, Lyle R, Deutsch S, Choudhury U, Bottani A, Antonarakis SE, Fryssira H, Dallapiccola B, Reymond A: Two high throughput technologies to detect segmental aneuploidies identify new Williams-Beuren syndrome patients with atypical deletions. J Med Genet. 2006, 43: 266-273. 10.1136/jmg.2005.034009. source

      Not checked in the free run.

    • cites [41] Osborne LR, Li M, Pober B, Chitayat D, Bodurtha J, Mandel A, Costa T, Grebe T, Cox S, Tsui LC, Scherer SW: A 1.5 million-base pair inversion polymorphism in families with Williams-Beuren syndrome. Nat Genet. 2001, 29: 321-325. 10.1038/ng753. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductnone given

    Procedures were approved by the Animal Ethics Committee of the University of Sydney and the Animal Ethics Committee of the Queensland Institute of Medical Research.

    “Procedures were approved by the Animal Ethics Committee of the University of Sydney and the Animal Ethics Committee of the Queensland Institute of Medical Research.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    A peptide blocking experiment was carried out for the Hdac1 amino terminus using sc-6299P.

    “A peptide blocking experiment was carried out for the Hdac1 amino terminus using sc-6299P (Santa Cruz Biotechnology).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    One of the hallmarks of epigenetic gene silencing across all multicellular organisms from plants to humans is the stochastic nature by which they operate.

    “One of the hallmarks of epigenetic gene silencing across all multicellular organisms from plants to humans is the stochastic nature by which they operate [45]”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [45] Martin DI, Whitelaw E: The vagaries of variegating transgenes. Bioessays. 1996, 18: 919-923. 10.1002/bies.950181111. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductcitation

    All quantitative RT-PCR reactions were performed in triplicate and normalized to both GAPDH and Rpl13A.

    “All reactions were performed in triplicate and normalized to both GAPDH and ribosomal highly basic 23-kDa protein (Rpl13A) [47].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [47] Mogal A, Abdulkadir SA: Effects of histone deacetylase inhibitor (HDACi); Trichostatin-A (TSA) on the expression of housekeeping genes. Mol Cell Probes. 2006, 20: 81-86. 10.1016/j.mcp.2005.09.008. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    To verify accuracy of the measurements, any landmarks showing marked differences between genotype groups were re-located on a separate day and the measurement repeated.

    “To verify accuracy of the measurements, any landmarks showing marked differences between genotype groups were re-located on a separate day and the measurement repeated.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    A sense probe was used in earlier experiments to confirm specificity of the antisense probe.

    “A sense probe was used in earlier experiments to confirm specificity of the antisense probe.”
    Quote in the paperNot a substantial claim
68 of 68

  • The authors state this as an assumption.

    Abnormal pale embryos at 17.5 dpc from MommeD7 intercrosses are homozygous for MommeD7.

    “Abnormal embryos are assumed to be homozygous for MommeD7.”

  • The paper relies on this without support.

    WBS is associated with a hemizygous deletion of approximately 28 genes in humans.

    “WBS is known to be associated with a hemizygous deletion of approximately 28 genes in humans”

  • The paper relies on this without support.

    Hdac1 and Baz1b are known to be involved in epigenetic processes.

    “Both are already known to be involved in epigenetic processes”
3 of 3

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • MommeD10 mapping interval has two reported end markers

    Minor

    Both descriptions start the MommeD10 interval at D5Mit165, but they name different markers at its other end.

  • MommeD9 mapping interval has two reported sizes

    Minor

    The mapping section gives a 3 Mb interval for MommeD9, while Table 4 gives 4 Mb.

2 of 2

Cites

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Authors
Ashe, A., Morgan, D. K., Whitelaw, N. C., Bruxner, T. J., Vickaryous, N. K., Cox, L. L., Butterfield, N. C., Wicking, C., Blewitt, M. E., Wilkins, S. J., Anderson, G. J., Cox, T. C., & Whitelaw, E.
Affiliations
  • QIMR Berghofer Medical Research Institute (AU)
  • The University of Queensland (AU)
  • University of Washington (US)
  • Walter and Eliza Hall Institute of Medical Research (AU)
Corresponding author
Whitelaw, Emma
ORCID
Venue
Genome Biology
Publisher
Springer Science and Business Media LLC
Published
2008-12-19
Volume
9
Issue
12
Pages
R182-R182
ISSN
  • 1465-6906 (ISSN-L)
  • 1474-760X
DOI
10.1186/gb-2008-9-12-r182
PMC
PMC2646286
OpenAlex
W2142568242
Cited by
117
References
48
Citations by year
2026: 2 · 2025: 1 · 2024: 8 · 2023: 3 · 2022: 7 · 2021: 7 · 2020: 4 · 2019: 6 · 2018: 5 · 2017: 5 · 2016: 7 · 2015: 6 · 2014: 10 · 2013: 12 · 2012: 14
FWCI
2.75
Type
journal article
Language
en
Open access
Licence
Locations
  • Genome biology (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Minerva Access (University of Melbourne) (submittedVersion, cc-by)
Funders
  • University of Sydney
  • National Health and Medical Research Council
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
Keywords
epigenetic silencing, modifier screen, N-ethyl-N-nitrosourea mutagenesis, SMCHD1, DNMT1, SNF2H, HDAC1, BAZ1B, Williams syndrome, developmental abnormalities, reproductive fitness, chromatin remodeling, histone deacetylase, mouse model
MeSH terms
Bromodomain Containing Proteins, Animals, Female, Genes, Lethal, Heterozygote, Histone Deacetylases, Male, Mice, Inbred C57BL, Mice, Inbred Strains, Mice, Transgenic, Transcription Factors, Genome, Williams Syndrome, Epigenesis, Genetic, Embryonic Development, Mice, Histone Deacetylase 1

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-10.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-10.

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