title: Characterization of two novel nuclear BTB/POZ domain zinc finger isoforms. Association with differentiation of hippocampal neurons, cerebellar granule cells, and macroglia.
abstract: 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.
authors.affiliation: Laboratory of Mammalian Molecular Genetics, The Panum Institute 6.5, University of Copenhagen, Blegdamsvej 3, DK-2200 Copenhagen N.
authors.forename: Cathy
authors.initials: C
authors.lastname: Mitchelmore
authors.forename: Karen M
authors.initials: KM
authors.lastname: Kjaerulff
authors.forename: Hans C
authors.initials: HC
authors.lastname: Pedersen
authors.forename: Jakob V
authors.initials: JV
authors.lastname: Nielsen
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Rasmussen
authors.forename: Mads F
authors.initials: MF
authors.lastname: Fisker
authors.forename: Bente
authors.initials: B
authors.lastname: Finsen
authors.forename: Karen M
authors.initials: KM
authors.lastname: Pedersen
authors.forename: Niels A
authors.initials: NA
authors.lastname: Jensen
mesh_terms: D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D002467:Cell Nucleus / Q000737:chemistry*; D002531:Cerebellum / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000378:metabolism; D015536:Down-Regulation; D015723:Gene Library; D005982:Glutathione Transferase / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D051379:Mice; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D009474:Neurons / Q000378:metabolism*; D010957:Plasmids / Q000378:metabolism; D020033:Protein Isoforms; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012097:Repressor Proteins / Q000737:chemistry*; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors; D020798:Two-Hybrid System Techniques; D016335:Zinc Fingers
chemical_list: C402243:ABTB1 protein, human; C509774:Abtb1 protein, mouse; D018076:DNA, Complementary; D020033:Protein Isoforms; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; C520426:Zbtb20 protein, mouse; D005982:Glutathione Transferase