In Embryonic Stem Cells, ZFP57/KAP1 Recognize a Methylated Hexanucleotide to Affect Chromatin and DNA Methylation of Imprinting Control Regions
Open accessAbstract
The maintenance of H3K9 and DNA methylation at imprinting control regions (ICRs) during early embryogenesis is key to the regulation of imprinted genes. Here, we reveal that ZFP57, its cofactor KAP1, and associated effectors bind selectively to the H3K9me3-bearing, DNA-methylated allele of ICRs in ES cells. KAP1 deletion induces a loss of heterochromatin marks at ICRs, whereas deleting ZFP57 or DNMTs leads to ICR DNA demethylation. Accordingly, we find that ZFP57 and KAP1 associated with DNMTs and hemimethylated DNA-binding NP95. Finally, we identify the methylated TGCCGC hexanucleotide as the motif that is recognized by ZFP57 in all ICRs and in several tens of additional loci, several of which are at least ZFP57-dependently methylated in ES cells. These results significantly advance our understanding of imprinting and suggest a general mechanism for the protection of specific loci against the wave of DNA demethylation that affects the mammalian genome during early embryogenesis.
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ZFP57 and its cofactor KAP1 bind selectively to nine DNA-methylated alleles of imprinting control regions in embryonic stem cells.
“ZFP57 and its cofactor KAP1 were shown to bind selectively to nine DNA-methylated alleles of imprinting control regions (ICRs) in ES cells43.”
From Transcription factors as readers and effectors of DNA methylation (2016) · cites this paper as [43]
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- Authors
- Quenneville, S., Verde, G., Corsinotti, A., Kapopoulou, A., Jakobsson, J., Offner, S., Baglivo, I., Pedone, P. V., Grimaldi, G., Riccio, A., & Trono, D.
- Affiliations
- École Polytechnique Fédérale de Lausanne (CH)
- Institute of Genetics and Biophysics (IT)
- University of Campania "Luigi Vanvitelli" (IT)
- Corresponding author
- Riccio, Andrea
- Trono, Didier
- ORCID
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2011-11
- Volume
- 44
- Issue
- 3
- Pages
- 361-372
- ISSN
- 1097-2765 (ISSN-L)
- PMC
- PMC3210328
- OpenAlex
- W2019127737
- Cited by
- 606
- References
- 44
- Citations by year
- 2026: 35 · 2025: 28 · 2024: 19 · 2023: 42 · 2022: 57 · 2021: 28 · 2020: 48 · 2019: 56 · 2018: 39 · 2017: 47 · 2016: 37 · 2015: 45 · 2014: 46 · 2013: 47 · 2012: 29
- FWCI
- 24.94
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Molecular Cell (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion, cc-by-nc-nd)
- Archivio Istituzionale della Ricerca - Università degli Studi della Campania "Luigi Vanvitelli" (submittedVersion)
- Lund University Publications (Lund University) (submittedVersion)
- Funders
- National Science Foundation
- European Commission
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
- Ministero dell’Istruzione, dell’Università e della Ricerca
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Syndromes and Imprinting
- 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
- Keywords
- ZFP57, KAP1, genomic imprinting, imprinting control regions, DNA methylation, H3K9me3, heterochromatin, embryonic stem cells, DNA methyltransferases, hemimethylated DNA, DNA demethylation, allele-specific methylation, early embryonic development
- MeSH terms
- Tripartite Motif-Containing Protein 28, Animals, Base Sequence, Binding Sites, Cell Line, Chromosomal Proteins, Non-Histone, Mice, Inbred C57BL, Molecular Sequence Data, Nuclear Proteins, Histone-Lysine N-Methyltransferase, Protein Methyltransferases, Repressor Proteins, DNA Modification Methylases, Genomic Imprinting, Gene Expression Regulation, Developmental, DNA Methylation, CCAAT-Enhancer-Binding Proteins, Chromatin Assembly and Disassembly, Ubiquitin-Protein Ligases, Mice, Embryonic Stem Cells, Gene Knockout Techniques, Nucleotide Motifs
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