Key Laboratory of Regenerative Biology of the Chinese Academy of Sciences and Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, 510530, Guangzhou, China.
Joint School of Life Sciences, Guangzhou Medical University and Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, 511436, Guangzhou, China.
Nat Commun. 2019 Jan 3;10(1):34. doi: 10.1038/s41467-018-08006-y.
The majority of mammalian genomes are devoted to transposable elements (TEs). Whilst TEs are increasingly recognized for their important biological functions, they are a potential danger to genomic stability and are carefully regulated by the epigenetic system. However, the full complexity of this regulatory system is not understood. Here, using mouse embryonic stem cells, we show that TEs are suppressed by heterochromatic marks like H3K9me3, and are also labelled by all major types of chromatin modification in complex patterns, including bivalent activatory and repressive marks. We identified 29 epigenetic modifiers that significantly deregulated at least one type of TE. The loss of Setdb1, Ncor2, Rnf2, Kat5, Prmt5, Uhrf1, and Rrp8 caused widespread changes in TE expression and chromatin accessibility. These effects were context-specific, with different chromatin modifiers regulating the expression and chromatin accessibility of specific subsets of TEs. Our work reveals the complex patterns of epigenetic regulation of TEs.
大多数哺乳动物基因组都致力于转座元件 (TEs)。虽然 TEs 因其重要的生物学功能而越来越受到重视，但它们对基因组稳定性构成潜在威胁，并受到表观遗传系统的精细调控。然而，这个调节系统的全部复杂性尚不清楚。在这里，我们使用小鼠胚胎干细胞表明 TEs 被 H3K9me3 等异染色质标记所抑制，并且还以复杂的模式被所有主要类型的染色质修饰标记，包括双价激活和抑制标记。我们鉴定了 29 种表观遗传修饰剂，它们至少显著调控了一种类型的 TE。Setdb1、Ncor2、Rnf2、Kat5、Prmt5、Uhrf1 和 Rrp8 的缺失导致 TE 表达和染色质可及性的广泛变化。这些影响具有特定的上下文，不同的染色质修饰剂调节特定 TE 子集的表达和染色质可及性。我们的工作揭示了 TEs 表观遗传调控的复杂模式。
