H4K16ac activates the transcription of transposable elements and contributes to their cis-regulatory function.
H4K16ac activates the transcription of transposable elements and contributes to their cis-regulatory function.
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DOI：
10.1038/s41594-023-01016-5
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发表时间：
2023-07
影响因子：
16.8
通讯作者：
Pradeepa, Madapura M.
中科院分区：
文献类型：
--
作者：
Pal, Debosree;Patel, Manthan;Boulet, Fanny;Sundarraj, Jayakumar;Grant, Olivia A.;Branco, Miguel R.;Basu, Srinjan;Santos, Silvia D. M.;Zabet, Nicolae Radu;Scaffidi, Paola;Pradeepa, Madapura M.
哺乳动物基因组含有丰富的转座因子（TE）及其残余物，许多表观遗传抑制机制制定沉默TE转录。然而，TE在早期发育、神经元谱系和癌症中上调，尽管导致TE转录的表观遗传因素尚未完全阐明。在这里，我们证明了男性特异性致死（MSL）复合物介导的组蛋白H4乙酰化在赖氨酸16（H4K16ac）是丰富的TE在人类胚胎干细胞（hESC）和癌细胞。这反过来激活全长长散布核元件（LINE1，L1）和内源性逆转录病毒（ERV）长末端重复序列（LTR）的子集的转录。此外，我们发现，H4K16ac标记的L1和LTR亚家族显示增强子样功能，并丰富了与活性增强子相关的染色质特征的基因组位置。重要的是，这些区域通常位于拓扑相关结构域的边界，并与基因形成环。基于CRISPR的表观遗传扰动和L1的遗传缺失揭示了H4K16ac标记的L1和LTR以顺式调节基因的表达。总体而言，富含H4K16ac的TE通过在TE处维持活性染色质景观而有助于特定基因组位置处的顺式调节景观。在这里，作者表明，某些转座因子（TE）的染色质在H4K16处被乙酰化包被，这可能导致局部染色质可及性和转录激活增加。反过来，这些乙酰化的TE显示增强子样的能力，以顺式调节基因表达。
Mammalian genomes harbor abundant transposable elements (TEs) and their remnants, with numerous epigenetic repression mechanisms enacted to silence TE transcription. However, TEs are upregulated during early development, neuronal lineage, and cancers, although the epigenetic factors contributing to the transcription of TEs have yet to be fully elucidated. Here, we demonstrate that the male-specific lethal (MSL)-complex-mediated histone H4 acetylation at lysine 16 (H4K16ac) is enriched at TEs in human embryonic stem cells (hESCs) and cancer cells. This in turn activates transcription of subsets of full-length long interspersed nuclear elements (LINE1s, L1s) and endogenous retrovirus (ERV) long terminal repeats (LTRs). Furthermore, we show that the H4K16ac-marked L1 and LTR subfamilies display enhancer-like functions and are enriched in genomic locations with chromatin features associated with active enhancers. Importantly, such regions often reside at boundaries of topologically associated domains and loop with genes. CRISPR-based epigenetic perturbation and genetic deletion of L1s reveal that H4K16ac-marked L1s and LTRs regulate the expression of genes in cis. Overall, TEs enriched with H4K16ac contribute to the cis-regulatory landscape at specific genomic locations by maintaining an active chromatin landscape at TEs. Here, the authors show that chromatin at certain transposable elements (TEs) is coated with acetylation at H4K16, which can lead to increased local chromatin accessibility and transcription activation. In turn, these acetylated TEs display enhancer-like capabilities to regulate gene expression in cis.
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影响因子：
5.8
作者：
Gu, Zuguang;Eils, Roland;Schlesner, Matthias
通讯作者：
Schlesner, Matthias
影响因子：
4.9
作者：
Hancks DC;Kazazian HH Jr
通讯作者：
Kazazian HH Jr
影响因子：
9.3
作者：
Durand NC;Shamim MS;Machol I;Rao SS;Huntley MH;Lander ES;Aiden EL
通讯作者：
Aiden EL
影响因子：
30.8
作者：
Jachowicz, Joanna W.;Bing, Xinyang;Torres-Padilla, Maria-Elena
通讯作者：
Torres-Padilla, Maria-Elena
影响因子：
9.2
作者：
Danecek P;Bonfield JK;Liddle J;Marshall J;Ohan V;Pollard MO;Whitwham A;Keane T;McCarthy SA;Davies RM;Li H
通讯作者：
Li H