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Cited by 91Genomics and Chromatin DynamicsHematopoietic Stem Cell TransplantationAcute Myeloid Leukemia Research

Use of RDA analysis of knockout mice to identify myeloid genes regulated in vivo by PU.1 and C/EBP

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Iwama, A., Zhang, P., Darlington, G. J., McKercher, S. R., Maki, R., Tenen, D. G.·1998·Nucleic Acids Research
DOI 10.1093/nar/26.12.3034PMC PMC147647
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Abstract

PU.1 and C/EBPalpha are transcription factors essential for normal myeloid development. Loss-of-function mutation of PU.1 leads to an absolute block in monocyte/macrophage development and abnormal granulocytic development while that of C/EBPalpha causes a selective block in neutrophilic differentiation. In order to understand these phenotypes, we studied the role of PU.1 and C/EBPalpha in the regulation of myeloid target genes in vivo . Northern blot analysis revealed that mRNAs encoding receptors for M-CSF, G-CSF and GM-CSF, were expressed at low levels in PU.1(-/-) fetal liver compared with wild type. To identify additional myeloid genes regulated by PU.1 and C/EBPalpha, we performed representational difference analysis (RDA), a PCR-based subtractive hybridization using fetal livers from wild type and PU.1 or C/EBPalpha knockout mice. By introducing a new modification of RDA, that of tissue-specific gene suppression, we could selectively identify a set of differentially expressed genes specific to myeloid cells. Differentially expressed genes included both primary and secondary granule protein genes. In addition, eight novel genes were identified that were upregulated in expression during myeloid differentiation. These methods provide a general strategy for elucidating the genes affected in murine knockout models.

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Crossref · 10.1093/nar/26.12.3034

Cites

63 of 63 references verified0 citation errors · 0 not checkable

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  • PU.1-deficient hematopoietic cells display minimal expression of G-CSF and GM-CSF receptors and no detectable M-CSF receptors.

    “PU.1-deficient hematopoietic cells display minimal expression of granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor receptors and no detectable M-CSF receptors (11,12).”

    From c-Jun Is a JNK-independent Coactivator of the PU.1 Transcription Factor (1999) · cites this paper as [12]

    The ‘mRNA expression of myeloid CSF receptors in mutant mice’ section reports markedly decreased G-CSF receptor mRNA and GM-CSF receptor mRNA undetectable by northern blot in PU.1-deficient fetal liver, although GM-CSF receptor mRNA had been detected by RT-PCR. Contrary to the claim’s last part, it reports that M-CSF receptor mRNA was decreased but detectable. The Discussion likewise says M-CSF and G-CSF receptors remained expressed at low levels. (LLM, conf=0.90)

    Experimental — accuracy not yet measured

  • c-Jun and the regulation of the M-CSF receptor by PU.1 both play important roles in the development of the monocytic lineage.

    “The transcription factor c-Jun (20 -24) and the regulation of the M-CSF receptor by the transcription factor PU.1 (11,12,55) both play important roles in the development of the monocytic lineage.”

    From c-Jun Is a JNK-independent Coactivator of the PU.1 Transcription Factor (1999) · cites this paper as [12]

    The Introduction says PU.1 regulates the M-CSF receptor promoter, and the receptor-expression section reports markedly decreased M-CSF receptor mRNA in PU.1-deficient fetal liver. But the Discussion says the role of myeloid CSF receptors in the developmental defects remains to be defined, so this paper does not establish that PU.1’s regulation of the receptor plays an important role in monocytic development. The c-Jun clause has separate citations and is not assessed against this source. (LLM, conf=0.88)

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Research works printed but not linked: 8

  1. Zhang,D.-E., Zhang,P., Wang,N.D., Hetherington,C.J., Darlington,G.J. and Tenen,D.G. (1997) Proc. Natl. Acad. Sci. USA, 94, 569-574.
  2. Voso,M.T., Burn,T.C., Wulf,G., Lim,B., Leone,G. and Tenen,D.G. (1994) Proc. Natl. Acad. Sci. USA, 91, 7932-7936.
  3. Ford,A.M., Bennett,C.A., Healy,L.E., Towatari,M., Greaves,M.F. and Enver,T. (1996) Proc. Natl. Acad. Sci. USA, 93, 10838-10843.
  4. Costa,R.H., Grayson,D.R., Xanthopoulos,K.G. and Darnell,J.E.,Jr (1988) Proc. Natl. Acad. Sci. USA, 85, 3840-3844.
  5. Radomska,H.S., Huettner,C.S., Zhang,P., Cheng,T., Scadden,D.T. and Tenen,D.G. (1998) Mol. Cell. Biol., in press.
  6. Yamanaka,R., Kim,G.-D., Radomska,H.S., Lekstrom-Himes,J., Smith,L.T., Antonson,P., Tenen,D.G. and Xanthopoulos,K.G. (1997) Proc. Natl. Acad. Sci. USA, 94, 6462-6467.
  7. Yamanaka,R., Barlow,C., Lekstrom-Himes,J., Castilia,L.H., Liu,P.P., Eckhaus,M., Decker,T., Wynshaw-Boris,A. and Xanthopoulos,K.G. (1997) Proc. Natl. Acad. Sci. USA, 94, 13187-13192.
  8. Cross,M., Mangelsdorf,I., Wedel,A. and Renkawitz,R. (1988) Proc. Natl. Acad. Sci. USA, 85, 6232-6236.

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Authors
Iwama, A., Zhang, P., Darlington, G. J., McKercher, S. R., Maki, R., & Tenen, D. G.
Affiliations
  • Beth Israel Deaconess Medical Center (US)
  • Baylor College of Medicine (US)
  • Sanford Burnham Prebys Medical Discovery Institute (US)
Corresponding author
Tenen, D. G.
ORCID
Venue
Nucleic Acids Research
Publisher
Oxford University Press (OUP)
Published
1998-06-01
Volume
26
Issue
12
Pages
3034-3043
ISSN
  • 0305-1048 (ISSN-L)
  • 1362-4962
DOI
10.1093/nar/26.12.3034
PMC
PMC147647
OpenAlex
W1977354830
Cited by
91
References
63
Citations by year
2023: 1 · 2019: 2 · 2016: 2 · 2015: 3 · 2014: 3
FWCI
2.67
Type
journal article
Language
en
Open access
Locations
  • Nucleic Acids Research (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • HighWire Press Open Archive (submittedVersion)
Funders
  • Japan Research Foundation for Clinical Pharmacology
  • Rural Development Administration
  • National Institutes of Health (5r01ai030656-08)
  • National Cancer Institute (CA 41456, R01CA041456)
  • National Institute of Allergy and Infectious Diseases (AI30656)
  • National Institute of Diabetes and Digestive and Kidney Diseases (R01DK048660, DK48660)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
  • Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
Keywords
PU.1, C/EBPα, myeloid development, transcription factors, knockout mice, representational difference analysis, fetal liver, granulocytic differentiation, M-CSF receptor, G-CSF receptor, GM-CSF receptor, granule proteins
MeSH terms
Proto-Oncogene Protein Spi-1, Animals, Cell Line, Transformed, Cloning, Molecular, Cytoplasmic Granules, DNA-Binding Proteins, Fetus, Genes, Liver, Molecular Sequence Data, Nuclear Proteins, Nucleic Acid Hybridization, Proto-Oncogene Proteins, RNA, Messenger, Transcription Factors, Trans-Activators, Polymerase Chain Reaction, Receptors, Colony-Stimulating Factor, Mice, Knockout, Gene Expression Regulation, Developmental, Leukopoiesis, CCAAT-Enhancer-Binding Proteins, Mice

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