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The C-terminal domain of Brd2 is important for chromatin interaction and regulation of transcription and alternative splicing
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SYSNO ASEP 0424234 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title The C-terminal domain of Brd2 is important for chromatin interaction and regulation of transcription and alternative splicing Author(s) Hnilicová, Jarmila (MBU-M) RID, ORCID
Hozeifi, S. (CZ)
Stejskalová, E. (CZ)
Dušková, E. (CZ)
Poser, I. (DE)
Humpolíčková, J. (CZ)
Hof, M. (CZ)
Staněk, D. (CZ)Source Title Molecular Biology of the Cell - ISSN 1059-1524
Roč. 24, č. 22 (2013), s. 3557-3568Number of pages 12 s. Language eng - English Country US - United States Keywords DOUBLE-BROMODOMAIN PROTEIN ; JUVENILE MYOCLONIC EPILEPSY ; LIVING CELLS Subject RIV EE - Microbiology, Virology R&D Projects GBP305/12/G034 GA ČR - Czech Science Foundation (CSF) Institutional support MBU-M - RVO:61388971 UT WOS 000328124600007 DOI 10.1091/mbc.E13-06-0303 Annotation Brd2 is a member of the bromodomain extra terminal (BET) protein family, which consists of four chromatin-interacting proteins that regulate gene expression. Each BET protein contains two N-terminal bromodomains, which recognize acetylated histones, and the C-terminal protein-protein interaction domain. Using a genome-wide screen, we identify 1450 genes whose transcription is regulated by Brd2. In addition, almost 290 genes change their alternative splicing pattern upon Brd2 depletion. Brd2 is specifically localized at promoters of target genes, and our data show that Brd2 interaction with chromatin cannot be explained solely by histone acetylation. Using coimmunoprecipitation and live-cell imaging, we show that the C-terminal part is crucial for Brd2 association with chromatin. Live-cell microscopy also allows us to map the average binding time of Brd2 to chromatin and quantify the contributions of individual Brd2 domains to the interaction with chromatin. Finally, we show that bromodomains and the C-terminal domain are equally important for transcription and splicing regulation, which correlates with the role of these domains in Brd2 binding to chromatin Workplace Institute of Microbiology Contact Eliška Spurná, eliska.spurna@biomed.cas.cz, Tel.: 241 062 231 Year of Publishing 2014
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