title: Signal-induced Brd4 release from chromatin is essential for its role transition from chromatin targeting to transcriptional regulation.
abstract: Bromodomain-containing protein Brd4 is shown to persistently associate with chromosomes during mitosis for transmitting epigenetic memory across cell divisions. During interphase, Brd4 also plays a key role in regulating the transcription of signal-inducible genes by recruiting positive transcription elongation factor b (P-TEFb) to promoters. How the chromatin-bound Brd4 transits into a transcriptional regulation mode in response to stimulation, however, is largely unknown. Here, by analyzing the dynamics of Brd4 during ultraviolet or hexamethylene bisacetamide treatment, we show that the signal-induced release of chromatin-bound Brd4 is essential for its functional transition. In untreated cells, almost all Brd4 is observed in association with interphase chromatin. Upon treatment, Brd4 is released from chromatin, mostly due to signal-triggered deacetylation of nucleosomal histone H4 at acetylated-lysine 5/8 (H4K5ac/K8ac). Through selective association with the transcriptional active form of P-TEFb that has been liberated from the inactive multi-subunit complex in response to treatment, the released Brd4 mediates the recruitment of this active P-TEFb to promoter, which enhances transcription at the stage of elongation. Thus, through signal-induced release from chromatin and selective association with the active form of P-TEFb, the chromatin-bound Brd4 switches its role to mediate the recruitment of P-TEFb for regulating the transcriptional elongation of signal-inducible genes.
authors: State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen 361005, Fujian, China.
authors: Nanping
authors: N
authors: Ai
authors: Xiangming
authors: X
authors: Hu
authors: Feng
authors: F
authors: Ding
authors: Bingfei
authors: B
authors: Yu
authors: Huiping
authors: H
authors: Wang
authors: Xiaodong
authors: X
authors: Lu
authors: Kai
authors: K
authors: Zhang
authors: Yannan
authors: Y
authors: Li
authors: Aidong
authors: A
authors: Han
authors: Wen
authors: W
authors: Lin
authors: Runzhong
authors: R
authors: Liu
authors: Ruichuan
authors: R
authors: Chen
mesh_terms: D000081:Acetamides / Q000494:pharmacology; D018797:Cell Cycle Proteins; D002460:Cell Line; D002843:Chromatin / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects; D042863:Cyclin-Dependent Kinase 9 / Q000378:metabolism; D005786:Gene Expression Regulation; D015497:HIV-1 / Q000235:genetics; D006367:HeLa Cells; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology; D006657:Histones / Q000378:metabolism; D006801:Humans; D007399:Interphase / Q000235:genetics; D008957:Models, Genetic; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D042925:Positive Transcriptional Elongation Factor B / Q000378:metabolism; D017384:Sequence Deletion; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects; D014466:Ultraviolet Rays; D000092468:Bromodomain Containing Proteins
chemical_list: D000081:Acetamides; D018797:Cell Cycle Proteins; D002843:Chromatin; D042863:Cyclin-Dependent Kinase 9; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D009687:Nuclear Proteins; D042925:Positive Transcriptional Elongation Factor B; D014157:Transcription Factors; C441289:BRD4 protein, human; D000092468:Bromodomain Containing Proteins; C014026:hexamethylene bisacetamide