The DOI matches its Crossref record; 26 of the 26 references it cites were found in a registry or an index.
CTCF maintains differential methylation at the Igf2/H19 locus
Abstract
Genomic imprinting relies on establishing and maintaining the parental-specific methylation of DNA elements that control the differential expression of maternal and paternal alleles. Although the essential DNA methyltransferases have been discovered, proteins that regulate the sequence-specific establishment and maintenance of allelic methylation have not been identified. One candidate regulator of methylation, the zinc-finger protein CTCF, binds to the imprinting control region (ICR) of the genes Igf2 (encoding insulin-like growth factor 2) and H19 (fetal liver mRNA; refs. 1,2). The unmethylated maternal ICR is a chromatin boundary that prevents distant enhancers from activating Igf2 (refs. 3-6). In vitro experiments have suggested that CTCF mediates boundary activity of the maternal ICR, and that methylation of the paternal ICR abolishes this activity by preventing CTCF binding. Using mice with point mutations in all four CTCF sites in the ICR, we show that maternally transmitted mutant ICRs in neonatal mice acquire a substantial but heterogeneous degree of methylation. Mutant ICRs in oocytes and blastocysts are not methylated, however, indicating that binding of CTCF is not required to establish the unmethylated ICR during oogenesis. We also show that the mutant ICR lacks enhancer-blocking activity, as the expression of Igf2 is activated on mutant maternal chromosomes. Conversely, maternal H19 expression is reduced, suggesting a positive role for CTCF in the transcription of that gene. This study constitutes the first in vivo demonstration of the multiple functions of CTCF in an ICR.
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“this study suggests that CTCF binding itself is necessary to maintain differential methylation of ICRs.”
From Transcription factors as readers and effectors of DNA methylation (2016) · cites this paper as [82]
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Cites
High sensitivity mapping of methylated cytosines
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Methylation of a CTCF-dependent boundary controls imprinted expression of the Igf2 gene
Bell, A. C., & Felsenfeld, G. (2000) · Nature · doi:10.1038/35013100 · Cited by 1,746
CTCF mediates methylation-sensitive enhancer-blocking activity at the H19/Igf2 locus
Hark, A. T., Schoenherr, C. J., Katz, D. J., Ingram, R. S., Levorse, J. M., & Tilghman, S. M. (2000) · Nature · doi:10.1038/35013106 · Cited by 1,547
Self-citationDnmt3L and the Establishment of Maternal Genomic Imprints
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Disruption of imprinting caused by deletion of the H19 gene region in mice
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Self-citationSpl elements protect a CpG island from de novo methylation
Brandeis, M., Frank, D., Keshet, I., Siegfried, Z., Mendelsohn, M. M., Names, A., Temper, V., Razin, A., & Cedar, H. (1994) · Nature · doi:10.1038/371435a0 · Cited by 719
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Sp1 sites in the mouse aprt gene promoter are required to prevent methylation of the CpG island.Preprint
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Kanduri, C., Pant, V., Loukinov, D., Pugacheva, E., Qi, C.-F., Wolffe, A., Ohlsson, R., & Lobanenkov, V. V. (2000) · Current Biology · doi:10.1016/s0960-9822(00)00597-2 · Cited by 444
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Metadata
- Authors
- Schoenherr, C. J., Levorse, J. M., & Tilghman, S. M.
- Affiliations
- University of Illinois Urbana-Champaign (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Schoenherr, Christopher J.
- Tilghman, Shirley M.
- Venue
- Nature Genetics
- Published
- 2002-12-02
- Volume
- 33
- Issue
- 1
- Pages
- 66-69
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- OpenAlex
- W2036636377
- Cited by
- 320
- References
- 26
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 4 · 2023: 4 · 2022: 6 · 2021: 7 · 2020: 10 · 2019: 7 · 2018: 7 · 2017: 9 · 2016: 10 · 2015: 14 · 2014: 9 · 2013: 15 · 2012: 22
- FWCI
- 13.84
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Genetics (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Syndromes and Imprinting
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Keywords
- CTCF, genomic imprinting, Igf2/H19 locus, imprinting control regions, DNA methylation, chromatin boundaries, enhancer blocking, maternal allele, oogenesis, blastocyst, IGF2 expression, zinc finger proteins
- MeSH terms
- CCCTC-Binding Factor, Alleles, Amino Acid Sequence, Animals, Animals, Newborn, Binding Sites, Blastocyst, Cell Line, DNA, DNA-Binding Proteins, Female, Gene Expression Regulation, Insulin-Like Growth Factor II, Male, Molecular Sequence Data, Mutation, Oocytes, Protein Binding, Repressor Proteins, RNA, Messenger, Sulfites, Transcription Factors, Genomic Imprinting, DNA Methylation, RNA, Untranslated, Mice, RNA, Long Noncoding
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