Chromatin states shaped by an epigenetic code confer regenerative potential to the mouse liver.
Chromatin states shaped by an epigenetic code confer regenerative potential to the mouse liver.
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由表观遗传密码形成的染色质状态赋予小鼠肝脏再生潜力。
DOI：
10.1038/s41467-021-24466-1
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发表时间：
2021-07-05
影响因子：
16.6
通讯作者：
Sadler KC
中科院分区：
文献类型：
--
作者：
Zhang C;Macchi F;Magnani E;Sadler KC
我们假设，对肝脏再生至关重要的高度受控的基因表达模式是由静止肝细胞中的表观遗传密码集编码的。在这里，我们报告了静止和再生小鼠肝脏的表观遗传学和转录组分谱定义了决定基因表达和转座子抑制的染色质状态。我们将组蛋白标记H3K4me3、H3K27me3和H3K9me3以及组蛋白变体H2 AZ的ATACseq和DNA甲基化分析与ChIPseq相结合，以识别具有不同功能特征的6种染色质状态。我们发现，参与增殖的基因存在于活跃状态，但被H3K27me3标记，并在静止的肝脏中沉默。我们发现，在再生过程中，H3K27me3的启动子被耗尽，促进了它们的动态表达。这些发现表明，静止肝脏中的肝脏染色质状态预示着基因的表达，促进再生的基因保持在活跃的染色质状态，但受到H3K27me3的抑制，允许在再生过程中做出快速和同步的反应。很少有研究提供再生肝脏表观遗传格局的功能分析。在这里，作者通过整合DNA甲基化、组蛋白修饰和染色质可及性的全基因组图谱，定义了静止和再生小鼠肝脏中的染色质状态，确定H3K27me3是一个赋予再生潜力的表观遗传标记。
We hypothesized that the highly controlled pattern of gene expression that is essential for liver regeneration is encoded by an epigenetic code set in quiescent hepatocytes. Here we report that epigenetic and transcriptomic profiling of quiescent and regenerating mouse livers define chromatin states that dictate gene expression and transposon repression. We integrate ATACseq and DNA methylation profiling with ChIPseq for the histone marks H3K4me3, H3K27me3 and H3K9me3 and the histone variant H2AZ to identify 6 chromatin states with distinct functional characteristics. We show that genes involved in proliferation reside in active states, but are marked with H3K27me3 and silenced in quiescent livers. We find that during regeneration, H3K27me3 is depleted from their promoters, facilitating their dynamic expression. These findings demonstrate that hepatic chromatin states in quiescent livers predict gene expression and that pro-regenerative genes are maintained in active chromatin states, but are restrained by H3K27me3, permitting a rapid and synchronized response during regeneration. Few studies have provided functional analysis of the epigenetic landscape in the regenerating liver. Here the authors define chromatin states in the quiescent vs. regenerating mouse liver through integration of genome wide profiles of DNA methylation, histone modifications, and chromatin accessibility, identifying H3K27me3 as an epigenetic mark conferring regenerative potential.
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DOI：
10.1038/nrm4043
发表时间：
2015-09
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
Du J;Johnson LM;Jacobsen SE;Patel DJ
通讯作者：
Patel DJ
DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
影响因子：
64.5
作者：
Benayoun BA;Pollina EA;Ucar D;Mahmoudi S;Karra K;Wong ED;Devarajan K;Daugherty AC;Kundaje AB;Mancini E;Hitz BC;Gupta R;Rando TA;Baker JC;Snyder MP;Cherry JM;Brunet A
通讯作者：
Brunet A
影响因子：
12.3
作者：
Akalin A;Kormaksson M;Li S;Garrett-Bakelman FE;Figueroa ME;Melnick A;Mason CE
通讯作者：
Mason CE
影响因子：
8
作者：
Chen, Tianyi;Oh, Sehhoon;Diehl, Anna Mae
通讯作者：
Diehl, Anna Mae