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DNA 甲基转移酶 3b 优先与浓缩染色质结合。

DNA methyltransferase 3b preferentially associates with condensed chromatin.

机构信息

Division of Gene Therapy Science, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan.

出版信息

Nucleic Acids Res. 2011 Feb;39(3):874-88. doi: 10.1093/nar/gkq870. Epub 2010 Oct 4.

DOI:10.1093/nar/gkq870
PMID:20923784
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3035464/
Abstract

In mammals, DNA methylation is catalyzed by DNA methyltransferases (DNMTs) encoded by Dnmt1, Dnmt3a and Dnmt3b. Since, the mechanisms of regulation of Dnmts are still largely unknown, the physical interaction between Dnmt3b and chromatin was investigated in vivo and in vitro. In embryonic stem cell nuclei, Dnmt3b preferentially associated with histone H1-containing heterochromatin without any significant enrichment of silent-specific histone methylation. Recombinant Dnmt3b preferentially associated with nucleosomal DNA rather than naked DNA. Incorporation of histone H1 into nucleosomal arrays promoted the association of Dnmt3b with chromatin, whereas histone acetylation reduced Dnmt3b binding in vitro. In addition, Dnmt3b associated with histone deacetylase SirT1 in the nuclease resistant chromatin. These findings suggest that Dnmt3b is preferentially recruited into hypoacetylated and condensed chromatin. We propose that Dnmt3b is a 'reader' of higher-order chromatin structure leading to gene silencing through DNA methylation.

摘要

在哺乳动物中，DNA 甲基化由 Dnmt1、Dnmt3a 和 Dnmt3b 编码的 DNA 甲基转移酶 (DNMTs) 催化。由于 Dnmts 的调节机制在很大程度上仍然未知，因此在体内和体外研究了 Dnmt3b 与染色质之间的物理相互作用。在胚胎干细胞核中，Dnmt3b 优先与含有组蛋白 H1 的异染色质结合，而沉默特异性组蛋白甲基化没有明显富集。重组 Dnmt3b 优先与核小体 DNA 而不是裸露 DNA 结合。组蛋白 H1 掺入核小体阵列促进了 Dnmt3b 与染色质的结合，而组蛋白乙酰化在体外降低了 Dnmt3b 的结合。此外，Dnmt3b 与核小体抗性染色质中的组蛋白去乙酰化酶 SirT1 相关。这些发现表明，Dnmt3b 优先被招募到低乙酰化和浓缩的染色质中。我们提出 Dnmt3b 是高级染色质结构的“读取器”，通过 DNA 甲基化导致基因沉默。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5340/3035464/6a0dd99cb00a/gkq870f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5340/3035464/2de89385f43b/gkq870f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5340/3035464/dba5be583b0e/gkq870f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5340/3035464/52640c128c4a/gkq870f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5340/3035464/ab97e019cd7f/gkq870f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5340/3035464/d9ae6cbec19c/gkq870f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5340/3035464/9fea3efb62f1/gkq870f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5340/3035464/6a0dd99cb00a/gkq870f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5340/3035464/2de89385f43b/gkq870f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5340/3035464/dba5be583b0e/gkq870f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5340/3035464/52640c128c4a/gkq870f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5340/3035464/ab97e019cd7f/gkq870f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5340/3035464/d9ae6cbec19c/gkq870f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5340/3035464/9fea3efb62f1/gkq870f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5340/3035464/6a0dd99cb00a/gkq870f7.jpg

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