دورية أكاديمية

DNA strand asymmetry generated by CpG hemimethylation has opposing effects on CTCF binding.

التفاصيل البيبلوغرافية
العنوان: DNA strand asymmetry generated by CpG hemimethylation has opposing effects on CTCF binding.
المؤلفون: Thomas SL; Department of Epigenetics, Van Andel Institute, Grand Rapids, MI 49503, USA., Xu TH; Department of Epigenetics, Van Andel Institute, Grand Rapids, MI 49503, USA.; Department of Structural Biology, Van Andel Institute, Grand Rapids, MI 49503, USA., Carpenter BL; Department of Epigenetics, Van Andel Institute, Grand Rapids, MI 49503, USA., Pierce SE; Department of Neurodegenerative Science, Van Andel Institute, Grand Rapids, MI 49503, USA., Dickson BM; Department of Epigenetics, Van Andel Institute, Grand Rapids, MI 49503, USA., Liu M; Department of Epigenetics, Van Andel Institute, Grand Rapids, MI 49503, USA., Liang G; Department of Urology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA., Jones PA; Department of Epigenetics, Van Andel Institute, Grand Rapids, MI 49503, USA.
المصدر: Nucleic acids research [Nucleic Acids Res] 2023 Jul 07; Vol. 51 (12), pp. 5997-6005.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Oxford University Press Country of Publication: England NLM ID: 0411011 Publication Model: Print Cited Medium: Internet ISSN: 1362-4962 (Electronic) Linking ISSN: 03051048 NLM ISO Abbreviation: Nucleic Acids Res Subsets: MEDLINE
أسماء مطبوعة: Publication: 1992- : Oxford : Oxford University Press
Original Publication: London, Information Retrieval ltd.
مواضيع طبية MeSH: CCCTC-Binding Factor*/metabolism , DNA Methylation* , Repressor Proteins*/metabolism, Animals ; Binding Sites ; Chromatin ; CpG Islands ; DNA/metabolism ; Mammals/genetics
مستخلص: CpG methylation generally occurs on both DNA strands and is essential for mammalian development and differentiation. Until recently, hemimethylation, in which only one strand is methylated, was considered to be simply a transitory state generated during DNA synthesis. The discovery that a subset of CCCTC-binding factor (CTCF) binding sites is heritably hemimethylated suggests that hemimethylation might have an unknown biological function. Here we show that the binding of CTCF is profoundly altered by which DNA strand is methylated and by the specific CTCF binding motif. CpG methylation on the motif strand can inhibit CTCF binding by up to 7-fold, whereas methylation on the opposite strand can stimulate binding by up to 4-fold. Thus, hemimethylation can alter binding by up to 28-fold in a strand-specific manner. The mechanism for sensing methylation on the opposite strand requires two critical residues, V454 and S364, within CTCF zinc fingers 7 and 4. Similar to methylation, CpG hydroxymethylation on the motif strand can inhibit CTCF binding by up to 4-fold. However, hydroxymethylation on the opposite strand removes the stimulatory effect. Strand-specific methylation states may therefore provide a mechanism to explain the transient and dynamic nature of CTCF-mediated chromatin interactions.
(© The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research.)
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معلومات مُعتمدة: R35 CA209859 United States CA NCI NIH HHS; R50 CA243878 United States CA NCI NIH HHS
المشرفين على المادة: 0 (CCCTC-Binding Factor)
0 (Chromatin)
9007-49-2 (DNA)
0 (Repressor Proteins)
تواريخ الأحداث: Date Created: 20230424 Date Completed: 20230724 Latest Revision: 20231116
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC10325916
DOI: 10.1093/nar/gkad293
PMID: 37094063
قاعدة البيانات: MEDLINE
الوصف
تدمد:1362-4962
DOI:10.1093/nar/gkad293