Characterization of two novel nuclear BTB/POZ domain zinc finger isoforms. Association with differentiation of hippocampal neurons, cerebellar granule cells, and macroglia.

BTB/POZ (broad complex tramtrack bric-a-brac/poxvirus and zinc finger) zinc finger factors are a class of nuclear DNA-binding proteins involved in development, chromatin remodeling, and cancer. However, BTB/POZ domain zinc finger factors linked to development of the mammalian cerebral cortex, cerebellum, and macroglia have not been described previously. We report here the isolation and characterization of two novel nuclear BTB/POZ domain zinc finger isoforms, designated HOF(L) and HOF(S), that are specifically expressed in early hippocampal neurons, cerebellar granule cells, and gliogenic progenitors as well as in differentiated glia. During embryonic development of the murine cerebral cortex, HOF expression is restricted to the hippocampal subdivision. Expression coincides with early differentiation of presumptive CA1 and CA3 pyramidal neurons and dentate gyrus granule cells, with a sharp decline in expression at the CA1/subicular border. By using bromodeoxyuridine labeling and immunohistochemistry, we show that HOF expression coincides with immature non-dividing cells and is down-regulated in differentiated cells, suggesting a role for HOF in hippocampal neurogenesis. Consistent with the postulated role of the POZ domain as a site for protein-protein interactions, both HOF isoforms are able to dimerize. The HOF zinc fingers bind specifically to the binding site for the related promyelocytic leukemia zinc finger protein as well as to a newly identified DNA sequence.     

真核生物中锌指蛋白的结构与功能

真核生物中的许多蛋白质分子包含锌指结构区,这类蛋白称为锌指蛋白.锌指蛋白因其包含特殊的指状结构,在对DNA、蛋白质和RNA的识别和结合中起重要作用.许多锌指蛋白的锌指结构域包含能与DNA特异结合的区域,并与某些效应结构域（如KRAB、SCAN、BTB/POZ、SNAG、SANT和PLAG等）相连,这类锌指蛋白常作为转录因子起作用,可调控靶基因的转录.一些锌指蛋白包含蛋白质识别结构域（如LIM锌指、MYND锌指、PHD锌指和RING锌指等）,它们能够特异地介导蛋白质之间的相互作用,因此被称作蛋白适配器.此外,某些锌指蛋白还可以结合RNA,起转录后调控作用.本文就锌指蛋白与DNA、RNA以及蛋白质分子间的相互作用作一综述.