Brd4 links chromatin targeting to HPV transcriptional silencing Journal Article
| Authors: | Wu, S. Y.; Lee, A. Y.; Hou, S. Y.; Kemper, J. K.; Erdjument-Bromage, H.; Tempst, P.; Chiang, C. M. |
| Article Title: | Brd4 links chromatin targeting to HPV transcriptional silencing |
| Abstract: | The E2 protein encoded by human papillomaviruses (HPVs) inhibits expression of the viral E6 oncoprotein, which, in turn, regulates p53 target gene transcription. To identify cellular proteins involved in E2-mediated transcriptional repression, we isolated an E2 complex from human cells conditionally expressing HPV-11 E2. Surprisingly, the double bromodomain-containing protein Brd4, which is implicated in cell cycle control and viral genome segregation, was found associated with E2 and conferred on E2 the ability to inhibit AP-1-dependent HPV chromatin transcription in an E2-binding site-specific manner as illustrated by in vitro reconstituted chromatin transcription experiments. Knockdown of Brd4 in human cells alleviates E2-mediated repression of HPV transcription. The E2-interacting domain at the extreme C terminus and the chromatin targeting activity of a bromodomain-containing region are both essential for the corepressor activity of Brd4. Interestingly, E2-Brd4 blocks the recruitment of TFIID and RNA polymerase II to the HPV E6 promoter region without inhibiting acetylation of nucleosomal histones H3 and H4, indicating an acetylation-dependent role of Brd4 in the recruitment of E2 for transcriptional silencing of HPV gene activity. Our finding that Brd4 is a component of the virus-assembled transcriptional silencing complex uncovers a novel function of Brd4 as a cellular cofactor modulating viral gene expression. © 2006 by Cold Spring Harbor Laboratory Press. |
| Keywords: | protein expression; unclassified drug; oncoprotein; human cell; promoter region; protein domain; animals; mice; gene targeting; reverse transcription polymerase chain reaction; carboxy terminal sequence; protein assembly; cell protein; transcription, genetic; in vitro study; hela cells; chromatin; histone h3; recombinant protein; oncogene proteins, fusion; binding site; gene silencing; cell cycle regulation; rna polymerase ii; acetylation; wart virus; gene activity; protein isolation; viral proteins; nucleosome; gene expression regulation, viral; histone h4; human papillomavirus; virus gene; transcription factor ap 1; human papillomavirus 18; hpv; papillomaviridae; gene segregation; human papillomavirus 11; ap-1; e2; brd4; chromatin transcription; protein brd4; transcription factor iid; human papillomavirus type 11; virus transcription |
| Journal Title: | Genes and Development |
| Volume: | 20 |
| Issue: | 17 |
| ISSN: | 0890-9369 |
| Publisher: | Cold Spring Harbor Laboratory Press |
| Date Published: | 2006-09-01 |
| Start Page: | 2383 |
| End Page: | 2396 |
| Language: | English |
| DOI: | 10.1101/gad.1448206 |
| PUBMED: | 16921027 |
| PROVIDER: | scopus |
| PMCID: | PMC1560413 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 58" - "Export Date: 4 June 2012" - "CODEN: GEDEE" - "Source: Scopus" |
