Identification of a novel BTB-zinc finger transcriptional repressor, CIBZ, that interacts with CtBP corepressor.
The transcriptional corepressor C-terminal binding protein (CtBP) is thought to be involved in development and oncogenesis, but the regulation of its corepressor activity is largely unknown. We show here that a novel BTB-zinc finger protein, CIBZ (CtBP-interacting BTB zinc finger protein; a mouse ortholog of rat ZENON that was recently identified as an e-box/dyad binding protein), redistributes CtBP to pericentromeric foci from a diffuse nuclear localization in interphase cells. CIBZ physically associates with CtBP via a conserved CtBP binding motif, PLDLR. When heterologously targeted to DNA, CIBZ represses transcription via two independent repression domains, an N-terminal BTB domain and a PLDLR motif-containing RD2 region, in a histone deacetylase-independent and -dependent manner, respectively. Mutation in the PLDLR motif abolishes the CIBZ-CtBP interaction and transcriptional repression activity of RD2, but does not affect the repression activity of the BTB domain. Furthermore, this PLDLR-mutated CIBZ cannot target CtBP to pericentromeric foci, although it is localized to the pericentromeric foci itself. These results suggest that at least one repression mechanism mediated by CIBZ is recruitment of the CtBP/HDAC complex to pericentromeric foci, and that CIBZ may regulate pericentromeric targeting of CtBP.
Sasai
Nobuhiro
N
Division of Gene Function in Animals, Nara Institute of Science and Technology, Ikoma, Nara 630-0192, Japan.
Matsuda
Eishou
E
Sarashina
Emiko
E
Ishida
Yasumasa
Y
Kawaichi
Masashi
M
D000199:Actins / Q000378:metabolism; D000429:Alcohol Oxidoreductases; D020816:Amino Acid Motifs; D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D006570:Heterochromatin; D006655:Histone Deacetylases / Q000737:chemistry / Q000378:metabolism; D051379:Mice; D008856:Microscopy, Fluorescence; D041681:NIH 3T3 Cells; D009419:Nerve Tissue Proteins / Q000378:metabolism; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D013045:Species Specificity; D014158:Transcription, Genetic; D014162:Transfection; D020798:Two-Hybrid System Techniques; D016335:Zinc Fingers / Q000235:genetics*
D000199:Actins; C510763:Zbtb38 protein, mouse; D004268:DNA-Binding Proteins; D006570:Heterochromatin; C484605:Nacc1 protein, mouse; D009419:Nerve Tissue Proteins; D010750:Phosphoproteins; D012097:Repressor Proteins; D000429:Alcohol Oxidoreductases; C096794:C-terminal binding protein; D006655:Histone Deacetylases