Histone deacetylase (HDAC) 1 and 2 complexes regulate both histone acetylation and crotonylation in vivo.
Histone deacetylase (HDAC) 1 and 2 complexes regulate both histone acetylation and crotonylation in vivo.
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DOI：
10.1038/s41598-018-32927-9
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发表时间：
2018-10-02
影响因子：
4.6
通讯作者：
Cowley SM
中科院分区：
文献类型：
--
作者：
Kelly RDW;Chandru A;Watson PJ;Song Y;Blades M;Robertson NS;Jamieson AG;Schwabe JWR;Cowley SM
组蛋白的蛋白质组学分析表明，它们经历了过量的酰化，其远远超出乙酰化，包括：巴豆酰化、丙酰化、丁酰化、丙二酰化、琥珀酰化、β-羟基丁酰化和2-羟基异丁酰化。到目前为止，许多功能数据集中在组蛋白巴豆酰化，类似于乙酰化，已与积极的基因调控，并加入了酰基转移酶，p300。尽管Sirtuins 1-3，沿着HDAC 3，已经显示在体外具有去巴豆酸酶活性，但是关于组蛋白巴豆酰化在体内的调节知之甚少。在这里，我们表明，组蛋白去乙酰化酶1和2（HDAC 1/2），催化核心的许多辅阻遏复合物，是重要的组蛋白去巴豆酸酶。HDAC 1/CoREST 1/LSD 1的三元复合物能够水解组蛋白H3 Lys 18-乙酰基（H3 K18 ac）和H3 Lys 18-巴豆酰基（H3 K18 cr）肽底物。ES细胞中HDAC 1/2的基因缺失增加了组蛋白巴豆酰化的总体水平，并导致总去巴豆酸酶活性降低85%。此外，我们使用ChIP-seq在有和没有HDAC 1/2的情况下定位了细胞中的H3 K18 cr，并观察到巴豆酰化水平增加，其在转录起始位点附近与H3 K18 ac在很大程度上重叠。总的来说，我们的数据表明，HDAC 1/2含有复合物是关键的调节剂组蛋白巴豆酰化在体内。
Proteomic analysis of histones has shown that they are subject to a superabundance of acylations, which extend far beyond acetylation, to include: crotonylation, propionylation, butyrylation, malonylation, succinylation, β-hydroxybutyrylation and 2-hydroxyisobutyrylation. To date, much of the functional data has focussed on histone crotonylation which, similar to acetylation, has been associated with positive gene regulation and is added by the acyltransferase, p300. Although Sirtuins 1–3, along with HDAC3, have been shown to possess decrotonylase activity in vitro, there is relatively little known about the regulation of histone crotonylation in vivo. Here we show that Histone Deacetylase 1 and 2 (HDAC1/2), the catalytic core of numerous co-repressor complexes, are important histone decrotonylase enzymes. A ternary complex of HDAC1/CoREST1/LSD1 is able to hydrolyse both histone H3 Lys18-acetyl (H3K18ac) and H3 Lys18-crotonyl (H3K18cr) peptide substrates. Genetic deletion of HDAC1/2 in ES cells increases global levels of histone crotonylation and causes an 85% reduction in total decrotonylase activity. Furthermore, we mapped H3K18cr in cells using ChIP-seq, with and without HDAC1/2, and observed increased levels of crotonylation, which largely overlaps with H3K18ac in the vicinity of transcriptional start sites. Collectively, our data indicate that HDAC1/2 containing complexes are critical regulators of histone crotonylation in vivo.
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影响因子：
4
作者：
Heinen CA;Jongejan A;Watson PJ;Redeker B;Boelen A;Boudzovitch-Surovtseva O;Forzano F;Hordijk R;Kelley R;Olney AH;Pierpont ME;Schaefer GB;Stewart F;van Trotsenburg AS;Fliers E;Schwabe JW;Hennekam RC
通讯作者：
Hennekam RC
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
影响因子：
14.8
作者：
Brand, Marjorie;Rampalli, Shravanti;Dilworth, F. Jeffrey
通讯作者：
Dilworth, F. Jeffrey
影响因子：
14.8
作者：
Dai, Lunzhi;Peng, Chao;Zhao, Yingming
通讯作者：
Zhao, Yingming
DOI：
10.1038/nrg2485
发表时间：
2009-01
期刊：
Nature reviews. Genetics
影响因子：
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