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望月 牧子
Department School of Medicine, School of Medicine Position Assistant Professor |
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| Article types | Original article |
| Language | English |
| Peer review | Peer reviewed |
| Title | Histone acetylation mediated by Brd1 is crucial for Cd8 gene activation during early thymocyte development. |
| Journal | Formal name：Nature communications Abbreviation：Nat Commun ISSN code：20411723/20411723 |
| Domestic / Foregin | Foregin |
| Volume, Issue, Page | 5,pp.5872 |
| Author and coauthor | 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 |
| Publication date | 2014/12 |
| Summary | 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. |
| DOI | 10.1038/ncomms6872 |
| PMID | 25519988 |