Histone acetylation mediated by Brd1 is crucial for Cd8 gene activation during early thymocyte development.
Histone acetylation mediated by Brd1 is crucial for Cd8 gene activation during early thymocyte development.
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DOI：
10.1038/ncomms6872
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发表时间：
2014-12-18
影响因子：
16.6
通讯作者：
Iwama, Atsushi
中科院分区：
文献类型：
--
作者：
Mishima, Yuta;Wang, Changshan;Miyagi, Satoru;Saraya, Atsunori;Hosokawa, Hiroyuki;Mochizuki-Kashio, Makiko;Nakajima-Takagi, Yaeko;Koide, Shuhei;Negishi, Masamitsu;Sashida, Goro;Naito, Taku;Ishikura, Tomoyuki;Onodera, Atsushi;Nakayama, Toshinori;Tenen, Daniel G.;Yamaguchi, Naoto;Koseki, Haruhiko;Taniuchi, Ichiro;Iwama, Atsushi
在T细胞发育过程中，Cd 8的表达通过其顺式调节增强子元件的动态调节来控制。增强子活性不足导致CD 4 + CD 8+双阳性（DP）胸腺细胞中的Cd 8表达多样化。Brd 1是Hbo 1组蛋白乙酰转移酶（HAT）复合物的亚基，负责组蛋白H3在赖氨酸14（H3 K14）处的乙酰化。在这里，我们发现造血祖细胞中Brd 1的缺失导致Cd 8的多样化表达，导致CD 4 + CD 8 −TCRβ−/低胸腺细胞的出现，在其性质上与DP胸腺细胞无法区分。生化分析证实，Brd 1与胸腺细胞中的Hbo 1形成HAT复合物。ChIP分析表明，Brd 1定位在Cd 8基因中的已知增强子处，并负责H3 K14处的乙酰化。这些研究结果表明，Brd 1介导的HAT活性是至关重要的有效激活Cd 8的表达通过乙酰化H3 K14，这作为一个表观遗传标记，促进招聘的转录机制的Cd 8增强子。
During T-cell development, Cd8 expression is controlled via dynamic regulation of its cis-regulatory enhancer elements. Insufficiency of enhancer activity causes variegated Cd8 expression in CD4 +CD8 + double-positive (DP) thymocytes. Brd1 is a subunit of the Hbo1 histone acetyltransferase (HAT) complex responsible for acetylation of histone H3 at lysine 14 (H3K14). Here we show that deletion of Brd1 in haematopoietic progenitors causes variegated expression of Cd8, resulting in the appearance of CD4 +CD8 −TCRβ−/low thymocytes indistinguishable from DP thymocytes in their properties. Biochemical analysis confirms that Brd1 forms a HAT complex with Hbo1 in thymocytes. ChIP analysis demonstrates that Brd1 localizes at the known enhancers in the Cd8 genes and is responsible for acetylation at H3K14. These findings indicate that the Brd1-mediated HAT activity is crucial for efficient activation of Cd8 expression via acetylation at H3K14, which serves as an epigenetic mark that promotes the recruitment of transcription machinery to the Cd8 enhancers.
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DOI：
10.1016/j.bbagrm.2014.03.001
发表时间：
2014-08
影响因子：
4.7
作者：
Rothbart, Scott B.;Strahl, Brian D.
通讯作者：
Strahl, Brian D.
影响因子：
16
作者：
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通讯作者：
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作者：
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通讯作者：
Yanagisawa, M
影响因子：
56.9
作者：
Mucida, Daniel;Park, Yunji;Cheroutre, Hilde
通讯作者：
Cheroutre, Hilde
影响因子：
64.8
作者：
Chi, TH;Wan, M;Crabtree, GR
通讯作者：
Crabtree, GR