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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 0422977 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název The C-terminal domain of Brd2 is important for chromatin interaction and regulation of transcription and alternative splicing Tvůrce(i) Hnilicová, Jarmila (UMG-J)
Hozeifi, Samira (UMG-J)
Stejskalová, Eva (UMG-J)
Dušková, Eva (UMG-J)
Poser, I. (DE)
Humpolíčková, Jana (UFCH-W) RID
Hof, Martin (UFCH-W) RID, ORCID
Staněk, David (UMG-J) RIDZdroj.dok. Molecular Biology of the Cell - ISSN 1059-1524
Roč. 24, č. 22 (2013), s. 3557-3568Poč.str. 12 s. Jazyk dok. eng - angličtina Země vyd. US - Spojené státy americké Klíč. slova Brd2 ; alternative splicing ; chromatin Vědní obor RIV EB - Genetika a molekulární biologie Vědní obor RIV – spolupráce Ústav fyzikální chemie J.Heyrovského - Fyzikální chemie a teoretická chemie CEP KAN200520801 GA AV ČR - Akademie věd GAP305/10/0424 GA ČR - Grantová agentura ČR GBP208/12/G016 GA ČR - Grantová agentura ČR GBP305/12/G034 GA ČR - Grantová agentura ČR Institucionální podpora UMG-J - RVO:68378050 ; UFCH-W - RVO:61388955 UT WOS 000328124600007 DOI 10.1091/mbc.E13-06-0303 Anotace 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. Pracoviště Ústav molekulární genetiky Kontakt Nikol Škňouřilová, nikol.sknourilova@img.cas.cz, Tel.: 241 063 217 Rok sběru 2014
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