In embryonic stem cells, ZFP57/KAP1 recognize a methylated hexanucleotide to affect chromatin and DNA methylation of imprinting control regions.
In embryonic stem cells, ZFP57/KAP1 recognize a methylated hexanucleotide to affect chromatin and DNA methylation of imprinting control regions.
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DOI：
10.1016/j.molcel.2011.08.032
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发表时间：
2011-11-04
期刊：
影响因子：
16
通讯作者：
Trono D
中科院分区：
文献类型：
--
作者：
Quenneville S;Verde G;Corsinotti A;Kapopoulou A;Jakobsson J;Offner S;Baglivo I;Pedone PV;Grimaldi G;Riccio A;Trono D
在胚胎发育早期，H3 K9和DNA甲基化在印迹控制区（ICR）的维持是印迹基因调控的关键。在这里，我们揭示了ZFP 57，它的辅因子KAP 1，和相关的效应选择性结合到H3 K9 me 3轴承，DNA甲基化的等位基因的ICR在ES细胞。KAP 1缺失诱导ICR处异染色质标记的丢失，而ZFP 57或DNMT缺失导致ICR DNA去甲基化。因此，我们发现ZFP 57和KAP 1与DNMT和半甲基化DNA结合NP 95相关。最后，我们确定了甲基化的TGCCGC六核苷酸作为在所有ICR和几十个额外的基因座中被ZFP 57识别的基序，其中几个在ES细胞中至少是ZFP 57依赖性甲基化的。这些结果显着推进我们的理解印记，并建议一个一般的机制，保护特定的位点对DNA去甲基化的浪潮，影响哺乳动物基因组在早期胚胎发生。ZFP 57/KAP 1结合ES细胞中的所有甲基化印迹控制区ZFP 57/KAP 1结合ES细胞中的其他非印迹甲基化序列ZFP 57/KAP 1是DNA和组蛋白甲基化维持所必需的ZFP 57识别具有两个C2 H2锌指的甲基化六核苷酸
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. ► ZFP57/KAP1 bind all methylated imprinted control regions in ES cells ► ZFP57/KAP1 bind other nonimprinted methylated sequences in ES cells ► ZFP57/KAP1 are necessary for DNA and histone methylation maintenance ► ZFP57 recognizes a methylated hexanucleotide with two C2H2 zinc fingers
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DOI：
10.1242/dev.030403
发表时间：
2009-06
期刊：
Development (Cambridge, England)
影响因子：
--
作者：
Koerner MV;Pauler FM;Huang R;Barlow DP
通讯作者：
Barlow DP
影响因子：
64.8
作者：
Hark, AT;Schoenherr, CJ;Tilghman, SM
通讯作者：
Tilghman, SM
影响因子：
9.2
作者：
Lehnertz, B;Ueda, Y;Peters, AHFM
通讯作者：
Peters, AHFM
影响因子：
56.9
作者：
Bostick, Magnolia;Kim, Jong Kyong;Jacobsen, Steven E.
通讯作者：
Jacobsen, Steven E.
影响因子：
4.8
作者：
Renda, Mario;Baglivo, Ilaria;Pedone, Paolo V.
通讯作者：
Pedone, Paolo V.