Defining heterochromatin in C. elegans through genome-wide analysis of the heterochromatin protein 1 homolog HPL-2.
Defining heterochromatin in C. elegans through genome-wide analysis of the heterochromatin protein 1 homolog HPL-2.
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DOI：
10.1101/gr.180489.114
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发表时间：
2015-01
期刊：
影响因子：
7
通讯作者：
Strome S
中科院分区：
文献类型：
--
作者：
Garrigues JM;Sidoli S;Garcia BA;Strome S
异染色质的形成在组织基因组和调节基因表达中起关键作用。在大多数生物中，异染色质位于着丝粒和端粒的两侧。为了识别大量研究的模型C中的异染色质区域。elegans，它具有分散的着丝粒的全着丝粒染色体，我们分析了异染色质蛋白1（HP 1）的直系同源物HPL-2的全基因组分布，并比较其分布与其他特征通常与异染色质。HPL-2结合与组蛋白H3在赖氨酸9处的单甲基化和二甲基化（H3 K9 me 1和H3 K9 me 2）高度相关，并在常染色体臂上形成广泛的结构域。尽管HPL-2与其他HP 1直系同源物一样，在体外结合H3 K9 me肽，但HPL-2在体内的分布在缺乏H3 K9 me的突变体胚胎中似乎相对正常，表明HPL-2的染色体分布可以以H3 K9 me非依赖性方式实现。与独立于H3 K9 me的HPL-2服务角色一致，hpl-2突变体蠕虫显示出比缺乏H3 K9 me的突变体蠕虫更严重的缺陷。HPL-2结合富集重复序列，并且在染色体臂上与着丝粒紧密相关。在基因水平上，HPL-2优先与表达良好的基因结合，HPL-2的缺失导致一些结合靶点的上调和其他结合靶点的下调。我们的工作定义了异染色质在一个重要的模式生物，并揭示了异染色质相对于其他系统的共享和独特的属性。
Formation of heterochromatin serves a critical role in organizing the genome and regulating gene expression. In most organisms, heterochromatin flanks centromeres and telomeres. To identify heterochromatic regions in the heavily studied model C. elegans, which possesses holocentric chromosomes with dispersed centromeres, we analyzed the genome-wide distribution of the heterochromatin protein 1 (HP1) ortholog HPL-2 and compared its distribution to other features commonly associated with heterochromatin. HPL-2 binding highly correlates with histone H3 mono- and dimethylated at lysine 9 (H3K9me1 and H3K9me2) and forms broad domains on autosomal arms. Although HPL-2, like other HP1 orthologs, binds H3K9me peptides in vitro, the distribution of HPL-2 in vivo appears relatively normal in mutant embryos that lack H3K9me, demonstrating that the chromosomal distribution of HPL-2 can be achieved in an H3K9me-independent manner. Consistent with HPL-2 serving roles independent of H3K9me, hpl-2 mutant worms display more severe defects than mutant worms lacking H3K9me. HPL-2 binding is enriched for repetitive sequences, and on chromosome arms is anticorrelated with centromeres. At the genic level, HPL-2 preferentially associates with well-expressed genes, and loss of HPL-2 results in up-regulation of some binding targets and down-regulation of others. Our work defines heterochromatin in an important model organism and uncovers both shared and distinctive properties of heterochromatin relative to other systems.
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