RESUMO
The activating transcription factor (ATF) family comprises a group of basic region-leucine zipper (bZIP) proteins, which have roles in the development of species as diverse as insects and mammals. Here we describe two novel mRNAs encoding a single, 30-kDa mouse polypeptide, designated mouse ATF5, which is 58% identical to mouse ATF4 in the carboxy-terminal bZIP region. Both transcripts harbor highly complex 5' untranslated regions that impede translation of the ATF5 open reading frame. The mouse and human ATF5 loci consist of at least four exons contained within 5 kb of genomic sequence. During mouse embryonic development, expression of Atf5 is pronounced at the late gestational period and appears to be confined to cells of the neuronal layers of the olfactory epithelium and vomeronasal organ. This suggests a role for ATF5 in odorant sensory neuron differentiation.
Assuntos
Neurônios Aferentes/metabolismo , Olfato/fisiologia , Fatores de Transcrição/genética , Fatores Ativadores da Transcrição , Processamento Alternativo/genética , Sequência de Aminoácidos , Animais , Sequência de Bases , Humanos , Camundongos , Dados de Sequência Molecular , Sintenia/genética , Fatores de Transcrição/metabolismo , Órgão Vomeronasal/metabolismoRESUMO
The immunophilin homolog FKBP8 has been implicated in the regulation of apoptosis. Here we show that the 38-kDa form of FKBP8 (FKBP38) derives from a truncated ORF. The extended FKBP8 ORFs are 46 and 44 kDa in mouse and 45 kDa in human. Although the genomic organization of mouse and human FKBP8 is evolutionarily conserved, additional first exons are encoded by the murine locus. A 4.4-kb murine Fkbp8 gene fragment, containing a GC-rich potential promoter, directed expression of a LacZ reporter gene to forebrain neurons in transgenic mice. Expression of the transgene was observed in CA1 pyramidal neurons of the hippocampus in transgenic mice from three lines. One transgenic founder mouse exhibited widespread forebrain expression of the LacZ transgene that resembles the pattern for the endogenous Fkbp8 gene. Thus promoter/enhancer elements for forebrain expression are located around the first exons of the mouse Fkbp8 gene.
Assuntos
Regiões Promotoras Genéticas/genética , Proteínas de Ligação a Tacrolimo/genética , Processamento Alternativo , Sequência de Aminoácidos , Animais , Sequência de Bases , Cerebelo/metabolismo , Corpo Estriado/metabolismo , DNA/química , DNA/genética , Éxons , Feminino , Expressão Gênica , Genes/genética , Hipocampo/metabolismo , Humanos , Hibridização In Situ , Íntrons , Óperon Lac/genética , Masculino , Camundongos , Camundongos Endogâmicos , Camundongos Transgênicos , Dados de Sequência Molecular , Neocórtex/metabolismo , Prosencéfalo/metabolismo , Isoformas de Proteínas/genética , Células Piramidais/metabolismo , Alinhamento de Sequência , Análise de Sequência de DNA , Homologia de Sequência de Aminoácidos , Homologia de Sequência do Ácido Nucleico , Sítio de Iniciação de TranscriçãoRESUMO
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.