The C-terminal domain of Brd2 is important for chromatin interaction and regulation of transcription and alternative splicing

0422977 - ÚMG 2014 RIV US eng J - Journal Article
Hnilicová, Jarmila - Hozeifi, Samira - Stejskalová, Eva - Dušková, Eva - Poser, I. - Humpolíčková, Jana - Hof, Martin - Staněk, David
The C-terminal domain of Brd2 is important for chromatin interaction and regulation of transcription and alternative splicing.
Molecular Biology of the Cell. Roč. 24, č. 22 (2013), s. 3557-3568. ISSN 1059-1524. E-ISSN 1939-4586
R&D Projects: GA AV ČR KAN200520801; GA ČR GAP305/10/0424; GA ČR GBP208/12/G016; GA ČR(CZ) GBP305/12/G034
Institutional support: RVO:68378050 ; RVO:61388955
Keywords : Brd2 * alternative splicing * chromatin
Subject RIV: EB - Genetics ; Molecular Biology; CF - Physical ; Theoretical Chemistry (UFCH-W)
Impact factor: 4.548, year: 2013

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.
Permanent Link: http://hdl.handle.net/11104/0229180