The homeodomain protein NK-3 recruits Groucho and a histone deacetylase complex to repress transcription.
Transcriptional repression by sequence-specific DNA binding factors is mediated by the recruitment of a corepressor complex to the promoter region. The NK-3 homeodomain protein is a transcriptional repressor that recruits the nuclear protein kinase, homeodomain interacting protein kinase 2 (HIPK2). Here we show that HIPK2 is a component of a corepressor complex containing Groucho and a histone deacetylase complex. Groucho, like HIPK2, acts as a corepressor for NK-3 and binds to NK-3 and HIPK2. Moreover, HIPK2 appears to regulate the corepressor activity of Groucho. Transcriptional repression by NK-3 and Groucho is relieved by the histone deacetylase inhibitor trichostatin A, and both NK-3 and Groucho directly interact with the histone deacetylase HDAC1 that is associated with mSin3A in vivo. Recruitment of the histone deacetylase complex by NK-3 decreases the acetylated histones that are associated with the target gene promoter. These results indicate that NK-3 represses transcription by recruiting a complex containing Groucho and a histone deacetylase complex that leads to histone modification on chromatin and suggest that HIPK2 may play a regulatory role in the corepressor complex formation.
Choi
C Y
CY
Laboratory of Molecular Cardiology, NHLBI, National Institutes of Health, Bethesda, Maryland 20892, USA.
Kim
Y H
YH
Kwon
H J
HJ
Kim
Y
Y
D001483:Base Sequence; D051792:Basic Helix-Loop-Helix Proteins; D002352:Carrier Proteins / Q000378:metabolism; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000378:metabolism*; D006367:HeLa Cells; D006655:Histone Deacetylases / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000378:metabolism*; D006801:Humans; D011494:Protein Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases; D012097:Repressor Proteins / Q000378:metabolism*; D014158:Transcription, Genetic
D051792:Basic Helix-Loop-Helix Proteins; D002352:Carrier Proteins; D017931:DNA Primers; D004268:DNA-Binding Proteins; D006655:Histone Deacetylases; D018398:Homeodomain Proteins; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D012097:Repressor Proteins; C091023:gro protein, Drosophila; C115114:HIPK2 protein, human