The homeodomain protein NK-3 recruits Groucho and a histone deacetylase complex to repress transcription

Transcriptional repression by sequence-specific DNA binding factors is medi ated by the recruitment of a corepressor complex to the promoter region. Th e 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 c orepressor for NK-3 and binds to NK-3 and HlPK2. Moreover, HIPK2 appears to regulate the corepressor activity of Groucho. Transcriptional repression b y NK-3 and Groucho is relieved by the histone deacetylase inhibitor trichos tatin A, and both NK-3 and Groucho directly interact with the histone deace tylase HDAC1 that is associated with mSin3A in vivo. Recruitment of the his tone 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 h istone deacetylase complex that leads to histone modification on chromatin and suggest that HIPK2 may play a regulatory role in the corepressor comple x formation.