Mechanism of polymerase II transcription repression by the histone variant macroH2A.
macroH2A (mH2A) is an unusual histone variant consisting of a histone H2A-like domain fused to a large nonhistone region. In this work, we show that histone mH2A represses p300- and Gal4-VP16-dependent polymerase II transcription, and we have dissected the mechanism by which this repression is realized. The repressive effect of mH2A is observed at the level of initiation but not at elongation of transcription, and mH2A interferes with p300-dependent histone acetylation. The nonhistone region of mH2A is responsible for both the repression of initiation of transcription and the inhibition of histone acetylation. In addition, the presence of this domain of mH2A within the nucleosome is able to block nucleosome remodeling and sliding of the histone octamer to neighboring DNA segments by the remodelers SWI/SNF and ACF. These data unambiguously identify mH2A as a strong transcriptional repressor and show that the repressive effect of mH2A is realized on at least two different transcription activation chromatin-dependent pathways: histone acetylation and nucleosome remodeling.
Doyen
Cécile-Marie
CM
Institut Albert Bonniot, INSERM U309, 38706 La Tronche cedex, France.
An
Woojin
W
Angelov
Dimitar
D
Bondarenko
Vladimir
V
Mietton
Flore
F
Studitsky
Vassily M
VM
Hamiche
Ali
A
Roeder
Robert G
RG
Bouvet
Philippe
P
Dimitrov
Stefan
S
D000107:Acetylation; D000818:Animals; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004257:DNA Polymerase II / Q000378:metabolism; D015536:Down-Regulation; D051548:Histone Acetyltransferases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006657:Histones / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism; D009707:Nucleosomes / Q000737:chemistry / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D012097:Repressor Proteins / Q000378:metabolism*; D015534:Trans-Activators / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014157:Transcription Factors / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014158:Transcription, Genetic; D014982:Xenopus laevis; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor
D018797:Cell Cycle Proteins; D004257:DNA Polymerase II; D051548:Histone Acetyltransferases; D006657:Histones; D009687:Nuclear Proteins; D009707:Nucleosomes; D012097:Repressor Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor; C070633:Gal-VP16; C120756:macroH2A histone