Unveiling RCOR1 as a rheostat at transcriptionally permissive chromatin.
Unveiling RCOR1 as a rheostat at transcriptionally permissive chromatin.
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DOI：
10.1038/s41467-022-29261-0
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发表时间：
2022-03-23
影响因子：
16.6
通讯作者：
Andrés ME
中科院分区：
文献类型：
--
作者：
Rivera C;Lee HG;Lappala A;Wang D;Noches V;Olivares-Costa M;Sjöberg-Herrera M;Lee JT;Andrés ME
RCOR 1是一种已知的转录抑制因子，其募集并定位染色质上的LSD 1和HDAC 1/2以消除组蛋白甲基化和乙酰化。然而，目前对RCOR 1的定位和功能的范围的理解是不完整的。在这里，我们探测RCOR 1的分布在全基因组范围内，意外地发现，RCOR 1主要与转录活性基因。生物化学分析表明，RCOR 1与RNA聚合酶II（POL-II）在转录过程中，脱乙酰化其羧基末端结构域（CTD）在赖氨酸7。我们提供的证据表明，这种非典型的RCOR 1活性与抑制POL-II生产性延伸活跃转录基因。因此，RCOR 1以两种方式抑制转录-第一，通过与HDAC缔合而擦除转录上允许的组蛋白修饰的经典机制，第二，通过使RNA POL-II的CTD脱乙酰化以抑制生产性延伸的非经典机制。我们得出结论，RCOR 1是一个转录变阻器。经典的神经元基因辅阻遏物RCOR 1/CoREST矛盾地富含转录活性染色质。在这里，作者表明RCOR 1在启动子近端暂停期间被招募，并负调控新生转录本的合成。他们还表明RCOR 1-LSD 1-HDAC 1复合物从RNA聚合酶II中去除赖氨酸乙酰化以抑制转录。
RCOR1 is a known transcription repressor that recruits and positions LSD1 and HDAC1/2 on chromatin to erase histone methylation and acetylation. However, there is currently an incomplete understanding of RCOR1’s range of localization and function. Here, we probe RCOR1’s distribution on a genome-wide scale and unexpectedly find that RCOR1 is predominantly associated with transcriptionally active genes. Biochemical analysis reveals that RCOR1 associates with RNA Polymerase II (POL-II) during transcription and deacetylates its carboxy-terminal domain (CTD) at lysine 7. We provide evidence that this non-canonical RCOR1 activity is linked to dampening of POL-II productive elongation at actively transcribing genes. Thus, RCOR1 represses transcription in two ways—first, via a canonical mechanism by erasing transcriptionally permissive histone modifications through associating with HDACs and, second, via a non-canonical mechanism that deacetylates RNA POL-II’s CTD to inhibit productive elongation. We conclude that RCOR1 is a transcription rheostat. The classical neuronal-gene corepressor RCOR1/CoREST is paradoxically enriched in transcriptionally active chromatin. Here the authors show RCOR1 is recruited during promoter-proximal pausing and negatively regulates the nascent-transcript synthesis. They also show that an RCOR1-LSD1- HDAC1 complex removes lysine acetylation from RNA polymerase II to repress transcription.
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DOI：
10.1016/j.tig.2016.03.005
发表时间：
2016-06
期刊：
Trends in genetics : TIG
影响因子：
--
作者：
Bagchi DN;Iyer VR
通讯作者：
Iyer VR
影响因子：
64.8
作者：
Ernst, Jason;Kheradpour, Pouya;Mikkelsen, Tarjei S.;Shoresh, Noam;Ward, Lucas D.;Epstein, Charles B.;Zhang, Xiaolan;Wang, Li;Issner, Robbyn;Coyne, Michael;Ku, Manching;Durham, Timothy;Kellis, Manolis;Bernstein, Bradley E.
通讯作者：
Bernstein, Bradley E.
影响因子：
4.5
作者：
Cusanovich DA;Pavlovic B;Pritchard JK;Gilad Y
通讯作者：
Gilad Y
影响因子：
8.8
作者：
Greer CB;Tanaka Y;Kim YJ;Xie P;Zhang MQ;Park IH;Kim TH
通讯作者：
Kim TH
影响因子：
16.6
作者：
Kalin JH;Wu M;Gomez AV;Song Y;Das J;Hayward D;Adejola N;Wu M;Panova I;Chung HJ;Kim E;Roberts HJ;Roberts JM;Prusevich P;Jeliazkov JR;Roy Burman SS;Fairall L;Milano C;Eroglu A;Proby CM;Dinkova-Kostova AT;Hancock WW;Gray JJ;Bradner JE;Valente S;Mai A;Anders NM;Rudek MA;Hu Y;Ryu B;Schwabe JWR;Mattevi A;Alani RM;Cole PA
通讯作者：
Cole PA