Abstract
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.
Highlights
Transcriptional repression by sequence-specific DNA binding factors is mediated by the recruitment of a corepressor complex to the promoter region
We have previously shown that the NK-3 homeodomain protein [15], which belongs to the NK-2 class that includes a large number of vertebrate homeodomain transcription factors [16], is a transcriptional repressor and that the nuclear protein
Because it was unknown whether Groucho is involved in the NK-3-mediated transcriptional repression, it was of interest to examine whether Groucho can act as a corepressor for NK-3
Summary
Transcriptional repression by sequence-specific DNA binding factors is mediated by the recruitment of a corepressor complex to the promoter region. We show that the NK-3 homeodomain transcription factor recruits the Groucho corepressor, HIPK2, and a histone deacetylase complex to repress transcription. 1 The abbreviations used are: HIPK2, homeodomain interacting protein kinase 2; aa, amino acid(s); CAT, chloramphenicol acetyltransferase; CHIP, chromatin immunoprecipitation; GFP, green fluorescent protein; GRO, Groucho; GST, glutathione S-transferase; HDAC, histone deacetylase; PCR, polymerase chain reaction; TSA, trichostatin A.
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