モチヅキ　マキコ   Mochidzuki Makiko   望月　牧子    所属   医学部 医学科    職種   助教
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	Histone acetylation mediated by Brd1 is crucial for Cd8 gene activation during early thymocyte development.
掲載誌名	正式名：Nature communications 略　 称：Nat Commun ISSNコード：20411723/20411723
掲載区分	国外
巻・号・頁	5,pp.5872
著者・共著者	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
発行年月	2014/12
概要	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