HP1-mediated silencing targets Pol II coactivator complexes.
Little is known of the specific biochemical mechanism by which heterochromatin protein 1 (HP1) inactivates a gene. We analyzed HP1-mediated inhibition of preinitiation complex (PIC) assembly in vitro on chromatin templates regulated by GAL4-VP16 or Sp1. HP1 blocked key subunits of the TFIID and Mediator coactivator complexes. Notably, binding of the same subunits was inhibited by HP1 on the Sp1-regulated survivin gene in vivo upon DNA damage-induced silencing.
Smallwood
Andrea
A
Department of Biological Chemistry, 351A Biomedical Sciences Research Building, David Geffen School of Medicine, University of California, Los Angeles, California 90095-1737, USA.
Black
Joshua C
JC
Tanese
Naoko
N
Pradhan
Sriharsa
S
Carey
Michael
M
D000090266:Chromobox Protein Homolog 5; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism*; D004257:DNA Polymerase II / Q000378:metabolism*; D020868:Gene Silencing; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D000077022:Survivin; D015534:Trans-Activators / Q000302:isolation & purification / Q000378:metabolism*; D035561:Transcription Factor TFIIA / Q000302:isolation & purification / Q000378:metabolism; D035362:Transcription Factor TFIID / Q000302:isolation & purification / Q000378:metabolism; D014158:Transcription, Genetic
C107489:BIRC5 protein, human; D002868:Chromosomal Proteins, Non-Histone; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D000077022:Survivin; D015534:Trans-Activators; D035561:Transcription Factor TFIIA; D035362:Transcription Factor TFIID; D000090266:Chromobox Protein Homolog 5; D004257:DNA Polymerase II