RESUMO
Two members of the d4 family of presumptive transcription modulators, neuro-d4 (Neud4) and ubi-d4/Requiem (Req), have been characterized previously. We cloned and characterized the third member of this gene family, cer-d4 (Cerd4), from chicken and mouse cDNA libraries. The expression patterns of Cerd4 gene in both species are similar and more restricted than expression patterns of other two d4 genes. The main sites of Cerd4 expression are retina and cerebellum, where multiple transcripts could be detected. Two major types of Cerd4 proteins are a full-length isoform possessing all domains characteristic to the d4 family and truncated XZ isoform without C-terminal tandem of PHD fingers. The developmental kinetics of expression of these isoforms is different. The intron/exon structure of human Cerd4 gene is similar to that of neuro-d4 and ubi-d4/Requiem genes, but most introns of Cerd4 gene are much larger than the corresponding introns of the other two genes.
Assuntos
Proteínas de Ligação a DNA/genética , Fatores de Transcrição/genética , Dedos de Zinco/genética , Sequência de Aminoácidos , Animais , Embrião de Galinha , Galinhas , Mapeamento Cromossômico , Clonagem Molecular , DNA/química , DNA/genética , DNA Complementar/química , DNA Complementar/genética , Éxons , Expressão Gênica , Regulação da Expressão Gênica no Desenvolvimento , Genes/genética , Íntrons , Camundongos , Camundongos Endogâmicos , Dados de Sequência Molecular , Alinhamento de Sequência , Análise de Sequência de DNA , Homologia de Sequência de AminoácidosAssuntos
Regulação da Expressão Gênica no Desenvolvimento , Família Multigênica , Gânglio Trigeminal/química , Dedos de Zinco/genética , Processamento Alternativo/genética , Sequência de Aminoácidos , Animais , Sequência de Bases , Northern Blotting , DNA/química , Sondas de DNA/química , Feminino , Biblioteca Gênica , Marcação de Genes , Masculino , Camundongos , Dados de Sequência Molecular , Mapeamento Físico do Cromossomo , RNA/química , Alinhamento de Sequência , Análise de Sequência de DNA , Homologia de Sequência de AminoácidosRESUMO
Synucleins are a family of small intracellular proteins expressed mainly in the nervous system. The involvement of synucleins in neurodegeneration and malignancy has been demonstrated, but the physiological functions of these proteins remain elusive. Further studies including generation of animals with modified persyn expression are necessary to clarify the functions of these proteins and the mechanisms of their involvement in human diseases. We cloned and determined the organization and chromosomal localization of the mouse gene coding for persyn, a member of the synuclein family. The gene is composed of five exons, and its general structure is very similar to that of the human persyn gene. Using fluorescence in situ hybridization, we assigned the persyn gene to the boundary of bands B and C on mouse chromosome 14. We found a fragment of the gene that directs expression of the persyn protein in sensory neurons and could be used for generation of transgenic animals.
Assuntos
Genes/genética , Proteínas de Neoplasias , Proteínas do Tecido Nervoso/genética , Células 3T3 , Animais , Cromossomos/genética , DNA/química , DNA/genética , Éxons , Regulação da Expressão Gênica , Hibridização in Situ Fluorescente , Íntrons , Camundongos , Dados de Sequência Molecular , Neurônios/metabolismo , Mapeamento Físico do Cromossomo , Análise de Sequência de DNA , gama-SinucleínaRESUMO
Persyn is a recently identified member of the synuclein family with a distinct pattern of expression during pre- and postnatal development of the mouse peripheral and central nervous systems. As with other synucleins, persyn is believed to be involved in the pathogenesis of human neurodegenerative diseases. However, in contrast to other synucleins, high levels of persyn mRNA expression were also found in advanced breast carcinomas, suggesting an involvement of the encoded protein in breast tumour progression. Here we have used an antibody specific to human persyn to demonstrate that the level of this protein is increased in ageing cerebral cortex and in breast tumours. We cloned, characterized and sequenced the human persyn genomic locus and localized it to the long arm of chromosome 10 in the q23.2-q23.3 region. Sequence information was used to search for specific mutations in the protein coding regions of persyn mRNA and the persyn gene in breast tumours and tumour cell lines. No tumour-specific mutations were found, but two linked polymorphisms in the coding region were detected, both in mRNA and exons III and IV of the gene. These results suggest that development of breast tumours correlates with overexpression of the wild-type persyn protein. Detailed characterization of the human persyn locus is important for further studies of the involvement of persyn in neurodegeneration and malignancy.
