RESUMO
Yin Yang 1 (YY1) is a protein that activates and represses transcription of a large number of cellular and viral genes. In addition, studies suggest that YY1 may play an important role in development and differentiation. Here, we report the isolation and analysis of a YY1 genomic clone from a lambda human liver library. Fluorescence in situ hybridization with the YY1 clone has localized the YY1 gene to chromosome 14 band q32. A major YY1 gene transcription initiation site has been mapped to 478 bp upstream of the ATG translation start site. The proximal promoter contains multiple Sp1 transcription factor binding sites but lacks a consensus TATA or CCAAT box. Transient transfections and detailed deletion analyses localized the promoter to no more than 277 bp upstream from the major transcription start site. Finally, we have found that overexpression of the adenovirus E1A protein represses expression of a reporter gene directed by the YY1 promoter.
Assuntos
Proteínas de Ligação a DNA/genética , Fatores de Transcrição/genética , Proteínas E1A de Adenovirus/genética , Sequência de Bases , Mapeamento Cromossômico , Cromossomos Humanos Par 14/genética , Clonagem Molecular , DNA/genética , Primers do DNA/genética , Fatores de Ligação de DNA Eritroide Específicos , Expressão Gênica , Genes Reporter , Humanos , Hibridização in Situ Fluorescente , Dados de Sequência Molecular , Reação em Cadeia da Polimerase , Regiões Promotoras Genéticas , Transfecção , Fator de Transcrição YY1RESUMO
Idiopathic generalized epilepsies account for about 40% of epilepsy up to age 40 and commonly have a genetic basis. One type is benign familial neonatal convulsions (BFNC), a dominantly inherited disorder of newborns. We have identified a sub-microscopic deletion of chromosome 20q13.3 that co-segregates with seizures in a BFNC family. Characterization of cDNAs spanning the deleted region identified one encoding a novel voltage-gated potassium channel, KCNQ2, which belongs to a new KQT-like class of potassium channels. Five other BFNC probands were shown to have KCNQ2 mutations, including two transmembrane missense mutations, two frameshifts and one splice-site mutation. This finding in BFNC provides additional evidence that defects in potassium channels are involved in the mammalian epilepsy phenotype.
Assuntos
Epilepsia/genética , Mutação , Canais de Potássio/genética , Sequência de Aminoácidos , Sequência de Bases , Linhagem Celular Transformada , Deleção Cromossômica , Cromossomos Humanos Par 20 , DNA Complementar , Feminino , Humanos , Recém-Nascido , Canal de Potássio KCNQ2 , Masculino , Dados de Sequência Molecular , Linhagem , Canais de Potássio de Abertura Dependente da Tensão da Membrana , Homologia de Sequência de AminoácidosRESUMO
A glutamate binding subunit gene, GRINA, has been previously mapped to human chromosome 8. A form of inherited epilepsy, benign familial neonatal convulsions (BFNC), has also been localized to chromosome 8. As NMDA receptors have been implicated in the pathogenesis of epilepsy, we were interested in determining whether GRINA mapped to the same region of chromosome 8 as BFNC. Fluorescence in situ hybridization localized GRINA to band 8q24, distal to the thyroglobulin gene. The strongest signal was seen at 8q24.3. A panel of 97 radiation hybrids (RH) was used to verify the localization. The RH mapping results placed GRINA as the most telomeric marker on our map of 8q24, distal to the interval defined for BFNC.