Transposable elements are regulated by context-specific patterns of chromatin marks in mouse embryonic stem cells
Transposable elements are regulated by context-specific patterns of chromatin marks in mouse embryonic stem cells
复制标题
转座元件受小鼠胚胎干细胞中染色质标记的特定模式调节
DOI：
10.1038/s41467-018-08006-y
复制
发表时间：
2019-01-03
影响因子：
16.6
通讯作者：
Hutchins, Andrew P.
中科院分区：
文献类型：
--
作者：
He, Jiangping;Fu, Xiuling;Hutchins, Andrew P.
大多数哺乳动物的基因组都是转座因子（TE）。虽然TE越来越多地被认为具有重要的生物学功能，但它们对基因组稳定性具有潜在的危险，并且受到表观遗传系统的精心调控。然而，这一监管体系的全部复杂性并不为人所知。在这里，使用小鼠胚胎干细胞，我们表明TE被异染色质标记如H3K9me3抑制，并且也被复杂模式中的所有主要类型的染色质修饰标记，包括二价激活和抑制标记。我们确定了29个表观遗传修饰，显着失调至少一种类型的TE。Setdb1、Ncor2、Rnf2、Kat5、Prmt 5、Uhrf1和Rrp8的缺失导致TE表达和染色质可及性的广泛变化。这些影响是特定的上下文，不同的染色质修饰剂调节表达和染色质可及性的特定子集的TE。我们的工作揭示了TEs表观遗传调控的复杂模式。
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 ofSetdb1,Ncor2,Rnf2,Kat5,Prmt5,Uhrf1, andRrp8caused 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.