Linker histone H1.2 establishes chromatin compaction and gene silencing through recognition of H3K27me3.
Linker histone H1.2 establishes chromatin compaction and gene silencing through recognition of H3K27me3.
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DOI：
10.1038/srep16714
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发表时间：
2015-11-19
影响因子：
4.6
通讯作者：
An W
中科院分区：
文献类型：
--
作者：
Kim JM;Kim K;Punj V;Liang G;Ulmer TS;Lu W;An W
连接蛋白H1是染色质的一种蛋白质成分，与高阶染色质压实和整体基因沉默有关。然而，越来越多的证据表明，H1起着基因特异性作用，调节相对较少的基因。在这里，我们发现H1亚型之一的H1.2在癌细胞中过度表达，并有助于基因沉默。H1.2以依赖于ezh2介导的H3K27me3的方式被募集到不同的染色质区域，并通过调节染色质结构抑制多种生长抑制基因的转录。H1.2的c端尾部对于观察到的效应至关重要，因为该结构域的三个H1.2特异性氨基酸的突变取消了H1.2结合H3K27me3核小体并使靶基因失活的能力。总的来说，这些结果为H1.2在染色质折叠调控中的功能提供了分子解释，并表明H3K27me3是调控H1.2在靶位点的募集和活性的关键机制。
Linker histone H1 is a protein component of chromatin and has been linked to higher-order chromatin compaction and global gene silencing. However, a growing body of evidence suggests that H1 plays a gene-specific role, regulating a relatively small number of genes. Here we show that H1.2, one of the H1 subtypes, is overexpressed in cancer cells and contributes to gene silencing. H1.2 gets recruited to distinct chromatin regions in a manner dependent on EZH2-mediated H3K27me3, and inhibits transcription of multiple growth suppressive genes via modulation of chromatin architecture. The C-terminal tail of H1.2 is critical for the observed effects, because mutations of three H1.2-specific amino acids in this domain abrogate the ability of H1.2 to bind H3K27me3 nucleosomes and inactivate target genes. Collectively, these results provide a molecular explanation for H1.2 functions in the regulation of chromatin folding and indicate that H3K27me3 is a key mechanism governing the recruitment and activity of H1.2 at target loci.