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Histone acetylation mediated by Brd1 is crucial for Cd8 gene activation during early thymocyte development.

ABSTRACT: 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(-)TCR?(-/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.

SUBMITTER: Mishima Y

PROVIDER: S-EPMC4490789 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature

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Histone acetylation mediated by Brd1 is crucial for Cd8 gene activation during early thymocyte development.

Mishima Yuta Y Wang Changshan C Miyagi Satoru S Saraya Atsunori A Hosokawa Hiroyuki H Mochizuki-Kashio Makiko M Nakajima-Takagi Yaeko Y Koide Shuhei S Negishi Masamitsu M Sashida Goro G Naito Taku T Ishikura Tomoyuki T Onodera Atsushi A Nakayama Toshinori T Tenen Daniel G DG Yamaguchi Naoto N Koseki Haruhiko H Taniuchi Ichiro I Iwama Atsushi A

Nature communications 20141218

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 ...[more]

PMID: 25519988

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Project description:Effector proteins are secreted by plant pathogens to enable host colonization. Typically, effector genes are tightly regulated, have very low expression levels in axenic conditions, and are strongly induced during host colonization. Chromatin remodeling contributes to the activation of effector genes in planta by still poorly known mechanisms. In this work, we investigated the role of histone acetylation in effector gene derepression in plant pathogens. We used Zymoseptoria tritici, a major pathogen of wheat, as a model to determine the role of lysine acetyltransferases (KATs) in plant infection. We showed that effector gene activation is associated with chromatin remodeling, featuring increased acetylation levels of histone H3 lysine 9 (H3K9) and 14 (H3K14) in effector loci. We functionally characterized the role of Z. tritici KATs and demonstrated their distinct contributions to growth, development, and infection. Sas3 is required for host colonization and pycnidia production and is involved in the acetylation of H3K9 and H3K14 in effector loci and, consequently, in effector gene activation during plant infection. We propose that Sas3-mediated histone acetylation is required for the spatiotemporal activation of effector genes and the virulence of Z. tritici. IMPORTANCE Pathogen infections require the production of effectors that enable host colonization. Effectors have diverse functions and are only expressed at certain stages of the infection cycle. Thus, effector genes are tightly regulated by several mechanisms, including chromatin remodeling. Here, we investigate the role of histone acetylation in effector gene activation in the fungal wheat pathogen Zymoseptoria tritici. We demonstrate that lysine acetyltransferases (KATs) are essential for the spatiotemporal regulation of effector genes. We show that the KAT Sas3 is involved in leaf symptom development and pycnidia formation. Importantly, our results indicate that Sas3 controls histone acetylation of effector loci and is a regulator of effector gene activation during stomatal penetration. Overall, our work demonstrates the key role of histone acetylation in regulating gene expression associated with plant infection.

Dataset Information

Histone acetylation mediated by Brd1 is crucial for Cd8 gene activation during early thymocyte development.

Publications

Histone acetylation mediated by Brd1 is crucial for Cd8 gene activation during early thymocyte development.

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