Transcriptional repression by sequence-specific DNA binding factors is mediated by the recruitment of a corepressor complex to the promoter region. The critical components of a corepressor complex are histone deacetylases that deacetylate core histones on chromatin, and corepressors that connect DNA-binding factors to the histone deacetylase complex. The NK-3 homeodomain protein (Bagpipe) belongs to the NK-2 class that includes a large number of vertebrate homeodomain transcription factors and plays an important role in visceral mesoderm development of Drosophila. As a transcriptional repressor, NK-3 directly interacts with the Groucho corepressor, and NK-3-mediated transcriptional repression either on the native promoter or on a synthetic promoter is greatly augmented by Groucho. In addition, transcriptional repression by NK-3 and Groucho is relieved by the histone deacetylase inhibitor trichostatin A. Immunoprecipitation experiments showed that both NK-3 and Groucho directly interacts with the histone deacetylase HDAC1 that is associated with mSin3A. Interaction domains of NK-3 and Groucho with HDAC1 coincide with the NK-3 repressor domain and the Groucho corepressor domain, respectively. Chromatin immunoprecipitation (CHIP) assays revealed that recruitment of the histone deacetylase complex by NK-3 decreases the acetylated histones (H3 and H4) which are associated with the target gene promoter. Taken together, these results provide firm evidence that the homeodomain transcription factor NK-3 (Bagpipe) represses transcription by recruiting a corepressor complex containing Groucho and a histone deacetylase complex that leads to histone modification on chromatin. - NK-3/bagpipe homeobox gene, Groucho, repressor, corepressor, histone deacetylase transcription
