The transcriptional regulation role of BRD7 by binding to acetylated histone through bromodomain.
Studies showed that the bromodomain binds to acetyl-lysines on histone tails, which is involved in deciphering the histone codes. BRD7, a novel bromodomain gene, is the first described bromodomain gene involved in nasopharyngeal carcinoma (NPC). Previous studies showed that ectopic expression of BRD7 inhibited cell growth and cell cycle progression from G1 to S phase in HNE1 cells (a NPC cell line) by transcriptionally regulating some cell cycle related genes including E2F3 gene. In the present study, we revealed the co-localization between acetylated H3 and BRD7 and found that the bromodomain of BRD7 is required for this co-localization. More importantly, wild-type BRD7 interacted with H3 peptide acetylated at Lys14, while the bromodomain deleted mutant lost this ability. We also found that the mutant BRD7 failed to regulate E2F3 promoter activity and inhibit cell cycle progression. These results indicated that the transcriptional regulation role of BRD7 was achieved by binding to acetylated histone H3 and that the bromodomain was essential for this role. In addition, no obvious changes were observed in the acetylated level of histone H3 after transfection with BRD7, indicating that chromatin remodeling, not chromatin modification, is the major mechanism of BRD7 mediated gene transcription. Taken together, the present work shed light on the fact that a novel bromodomain gene, BRD7, is of importance in transcriptional regulation and cellular events including cell cycle.
Peng
Cong
C
Cancer Research Institution, Central of South University, Changsha, Hunan, China.
Zhou
Jie
J
Liu
Hua Ying
HY
Zhou
Ming
M
Wang
Li Li
LL
Zhang
Qiu Hong
QH
Yang
Yi Xin
YX
Xiong
Wei
W
Shen
Shou Rong
SR
Li
Xiao Ling
XL
Li
Gui Yuan
GY
D000107:Acetylation; D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D002453:Cell Cycle / Q000235:genetics; D002522:Chlorocebus aethiops; D002868:Chromosomal Proteins, Non-Histone / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D050699:E2F3 Transcription Factor / Q000235:genetics*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D051548:Histone Acetyltransferases / Q000378:metabolism; D006657:Histones / Q000378:metabolism*; D006877:Hydroxamic Acids / Q000494:pharmacology*; D018613:Microscopy, Confocal; D008969:Molecular Sequence Data; D009154:Mutation; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D011485:Protein Binding; D016415:Sequence Alignment; D017384:Sequence Deletion; D014158:Transcription, Genetic; D000092468:Bromodomain Containing Proteins
D002868:Chromosomal Proteins, Non-Histone; D050699:E2F3 Transcription Factor; D004791:Enzyme Inhibitors; D051548:Histone Acetyltransferases; D006657:Histones; D006877:Hydroxamic Acids; D009687:Nuclear Proteins; C485694:BRD7 protein, human; D000092468:Bromodomain Containing Proteins; C098319:E2F3 protein, human; C012589:trichostatin A