Transcriptional regulation of a novel BTB-zinc finger protein GetB (CIBZ)

转录辅阻遏物C-末端结合蛋白（CtBP）被认为参与发育和肿瘤发生，但其辅阻遏物活性的调节在很大程度上是未知的。我们在这里表明，一种新的BTB-锌指蛋白，CIBZ（CtBP相互作用的BTB锌指蛋白），重新分配CtBP从一个弥漫性的核定位在间期细胞的着丝粒灶。CIBZ通过保守的CtBP结合基序PLDLR与CtBP物理缔合。当异源靶向DNA时，CIBZ通过两个独立的阻遏结构域（N-末端BTB结构域和含PLDLR基序的RD 2区域）分别以组蛋白脱乙酰酶独立和依赖的方式抑制转录。PLDLR基序中的突变消除了RD 2的CIBZ-CtBP相互作用和转录抑制活性，但不影响BTB结构域的抑制活性。此外，这种PLDLR突变的CIBZ不能将CtBP靶向至着丝粒周围病灶，尽管其定位于着丝粒周围病灶本身。这些结果表明，CIBZ介导的至少一种抑制机制是CtBP/HDAC复合物向着丝粒周围病灶的募集，并且CIBZ可以调节CtBP的着丝粒周围靶向。

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), 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 perioentromeric foci, and that CIBZ may regulate pericentromeric targeting of CtBP.