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The C-terminal domain of Brd2 is important for chromatin interaction and regulation of transcription and alternative splicing.
- Source :
-
Molecular biology of the cell [Mol Biol Cell] 2013 Nov; Vol. 24 (22), pp. 3557-68. Date of Electronic Publication: 2013 Sep 18. - Publication Year :
- 2013
-
Abstract
- 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.
- Subjects :
- Alternative Splicing
HeLa Cells
Histones metabolism
Humans
Microscopy, Video
Promoter Regions, Genetic
Protein Binding
Protein Serine-Threonine Kinases metabolism
Protein Structure, Tertiary
Recombinant Fusion Proteins genetics
Recombinant Fusion Proteins metabolism
Signal Transduction
Transcription Factors
Transcription, Genetic
Chromatin metabolism
Gene Expression Regulation
Genome, Human
Histones genetics
Protein Serine-Threonine Kinases genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1939-4586
- Volume :
- 24
- Issue :
- 22
- Database :
- MEDLINE
- Journal :
- Molecular biology of the cell
- Publication Type :
- Academic Journal
- Accession number :
- 24048450
- Full Text :
- https://doi.org/10.1091/mbc.E13-06-0303