Characterization of HRG22, a human homologue of the putative tumor suppressor gene HIC1

Database searches identified on chromosome 22q11.2, a region subject to tra nslocations, an homologue of the HIC1 (hypermethylated in cancer) candidate tumor suppressor gene located at 17p13.3. This gene was termed HRG22 for H IC1-related gene on chromosome 22. We have characterized a new HRG22 upstre am coding exon and defined the complete coding sequence of the human and ze brafish HRG22 genes. Alignment of the HRG22 and HIC1 proteins from various species revealed high sequence homology in their N-terminal BTB/POZ and fiv e C-terminal C2H2 zinc finger domains and highlighted a conserved GLDLSKK/R peptide in their middle region. The full-length HRG22 and HIC1 proteins co localize onto nuclear dots and share several functional properties since th eir BTB/POZ domains heterodimerize and are autonomous transcriptional repre ssion domain insensitive to Trichostatin A, a histone deacetylase (HDAC) in hibitor. Thus, HIC1 and HRG22 define a subgroup of BTB/POZ domains unable t o recruit repressing complexes containing an HDAC activity. (C) 2001 Academ ic Press.