Analysis of the structure and function of the transcriptional coregulator HOP.

摘要: Homeodomain-only protein (HOP) is an 8-kDa transcriptional corepressor that essential for the normal development of mammalian heart. Previous studies have shown HOP, which consists entirely a putative homeodomain, acts downstream Nkx2.5 and associates with serum response factor (SRF), repressing transcription from SRF-responsive genes. HOP also able to recruit histone deacetylase (HDAC) activity, consistent its ability repress transcription. Unlike other classic homeodomain proteins, does not appear interact DNA, although it has been unclear if this because overall divergent structure or specific amino acid differences between homeodomains. To work toward understanding function, we determined 3D full-length used range biochemical assays define parts are functionally important repression activity. We show forms classical fold but cannot recognize double stranded result emphasizes importance caution in predicting function sequence homology alone. demonstrate two distinct regions on surface required SRF-driven reporter gene, likely these motifs direct interactions partner proteins such as SRF- HDAC-containing complexes. Our results co-opted during evolution functions than sequence-specific DNA binding suggest adaptor mediate repression.