Institute of Molecular Biology of Barcelona, IBMB, CSIC, Baldiri Reixac 4, 08028 Barcelona, Spain.
Institute for Research in Biomedicine of Barcelona, IRB Barcelona. The Barcelona Institute of Science and Technology. Baldiri Reixac 10, 08028 Barcelona, Spain.
Nucleic Acids Res. 2022 Sep 9;50(16):9212-9225. doi: 10.1093/nar/gkac716.
Post-translational modifications (PTMs) of core histones are important epigenetic determinants that correlate with functional chromatin states. However, despite multiple linker histone H1s PTMs have been identified, little is known about their genomic distribution and contribution to the epigenetic regulation of chromatin. Here, we address this question in Drosophila that encodes a single somatic linker histone, dH1. We previously reported that dH1 is dimethylated at K27 (dH1K27me2). Here, we show that dH1K27me2 is a major PTM of Drosophila heterochromatin. At mitosis, dH1K27me2 accumulates at pericentromeric heterochromatin, while, in interphase, it is also detected at intercalary heterochromatin. ChIPseq experiments show that >98% of dH1K27me2 enriched regions map to heterochromatic repetitive DNA elements, including transposable elements, simple DNA repeats and satellite DNAs. Moreover, expression of a mutated dH1K27A form, which impairs dH1K27me2, alters heterochromatin organization, upregulates expression of heterochromatic transposable elements and results in the accumulation of RNA:DNA hybrids (R-loops) in heterochromatin, without affecting H3K9 methylation and HP1a binding. The pattern of dH1K27me2 is H3K9 methylation independent, as it is equally detected in flies carrying a H3K9R mutation, and is not affected by depletion of Su(var)3-9, HP1a or Su(var)4-20. Altogether these results suggest that dH1K27me2 contributes to heterochromatin organization independently of H3K9 methylation.
核心组蛋白的翻译后修饰（PTMs）是重要的表观遗传决定因素，与功能性染色质状态相关。然而，尽管已鉴定出多种连接组蛋白H1的PTMs，但对其基因组分布以及对染色质表观遗传调控的贡献却知之甚少。在这里，我们在编码单个体细胞连接组蛋白dH1的果蝇中解决了这个问题。我们之前报道过dH1在K27位点发生二甲基化（dH1K27me2）。在这里，我们表明dH1K27me2是果蝇异染色质的主要PTM。在有丝分裂时，dH1K27me2在着丝粒周围异染色质处积累，而在间期，在居间异染色质中也能检测到。ChIPseq实验表明，>98%的dH1K27me2富集区域定位于异染色质重复DNA元件，包括转座元件、简单DNA重复序列和卫星DNA。此外，表达一种损害dH1K27me2的突变型dH1K27A形式，会改变异染色质组织，上调异染色质转座元件的表达，并导致RNA:DNA杂交体（R环）在异染色质中积累，而不影响H3K9甲基化和HP1a结合。dH1K27me2的模式独立于H3K9甲基化，因为在携带H3K9R突变的果蝇中同样能检测到，并且不受Su(var)3-9、HP1a或Su(var)4-20缺失的影响。总之，这些结果表明dH1K27me2独立于H3K9甲基化对异染色质组织起作用。
