Simultaneous epigenetic perturbation and genome imaging reveal distinct roles of H3K9me3 in chromatin architecture and transcription.
Simultaneous epigenetic perturbation and genome imaging reveal distinct roles of H3K9me3 in chromatin architecture and transcription.
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DOI：
10.1186/s13059-020-02201-1
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发表时间：
2020-12-08
期刊：
影响因子：
12.3
通讯作者：
Ma H
中科院分区：
文献类型：
--
作者：
Feng Y;Wang Y;Wang X;He X;Yang C;Naseri A;Pederson T;Zheng J;Zhang S;Xiao X;Xie W;Ma H
尽管H3 K9 me 3、染色质结构和转录抑制之间存在长期观察到的相关性，但H3 K9 me 3如何调节活细胞中基因组的高阶组织和转录活性仍不清楚。在这里，我们开发了EpiGo（表观遗传扰动诱导的基因组组织）-KRAB，以在人类19号染色体上跨越数百个基因座的数百个位点上引入H3 K9 me 3，并同时跟踪基因组组织。EpiGo-KRAB足以诱导基因组聚类和从头异染色质样结构域形成，这需要SETDB 1，H3 K9 me 3的甲基转移酶。出乎意料的是，EpiGo-KRAB诱导的异染色质样结构域不会导致广泛的基因阻遏，除了一小部分基因同时丢失H3 K4 me 3和H3 K27 ac。异位H3 K9 me 3似乎在非活性区域中扩散，但在很大程度上限制于活性区域中的转录起始位点。最后，Hi-C分析表明EpiGo-KRAB主要在隔室边界重塑现有隔室。这些结果表明H3 K9 me 3在基因组组织中的作用可以部分地与其在基因阻遏中的功能分开。补充信息随附于10.1186/s13059-020-02201-1。
Despite the long-observed correlation between H3K9me3, chromatin architecture, and transcriptional repression, how H3K9me3 regulates genome higher-order organization and transcriptional activity in living cells remains unclear. Here, we develop EpiGo (Epigenetic perturbation induced Genome organization)-KRAB to introduce H3K9me3 at hundreds of loci spanning megabases on human chromosome 19 and simultaneously track genome organization. EpiGo-KRAB is sufficient to induce genomic clustering and de novo heterochromatin-like domain formation, which requires SETDB1, a methyltransferase of H3K9me3. Unexpectedly, EpiGo-KRAB-induced heterochromatin-like domain does not result in widespread gene repression except a small set of genes with concurrent loss of H3K4me3 and H3K27ac. Ectopic H3K9me3 appears to spread in inactive regions but is largely restricted from transcriptional initiation sites in active regions. Finally, Hi-C analysis showed that EpiGo-KRAB reshapes existing compartments mainly at compartment boundaries. These results reveal the role of H3K9me3 in genome organization could be partially separated from its function in gene repression. Supplementary information accompanies this paper at 10.1186/s13059-020-02201-1.
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影响因子：
12.3
作者：
Fortin JP;Hansen KD
通讯作者：
Hansen KD
影响因子：
48
作者：
Ma H;Tu LC;Naseri A;Chung YC;Grunwald D;Zhang S;Pederson T
通讯作者：
Pederson T
影响因子：
64.8
作者：
Dixon JR;Jung I;Selvaraj S;Shen Y;Antosiewicz-Bourget JE;Lee AY;Ye Z;Kim A;Rajagopal N;Xie W;Diao Y;Liang J;Zhao H;Lobanenkov VV;Ecker JR;Thomson JA;Ren B
通讯作者：
Ren B
DOI：
10.1073/pnas.1420024112
发表时间：
2015-03-10
影响因子：
11.1
作者：
Ma, Hanhui;Naseri, Ardalan;Pederson, Thoru
通讯作者：
Pederson, Thoru
影响因子：
64.8
作者：
Falk, Martin;Feodorova, Yana;Mirny, Leonid A.
通讯作者：
Mirny, Leonid A.