RESUMEN
POU homeodomain proteins are important regulators of ubiquitous as well as tissue-specific transcription. Ubiquitously expressed Oct-1 and tissue-specific Oct-2 proteins are members of the POU family and contain very similar DNA-binding POU domains. While Oct-1 is ubiquitous, Oct-2 is predominantly expressed in B cells, in activated T cells and in nervous system. Oct-1 is involved in regulation of some houskeeping genes-histone H2B, snRNAs as well as in tissue-specific regulation of immunoglobuline gene transcription and of some other genes. Here we report that novel alternatively spliced product of the human Oct-1 gene encode Oct-1L isoform with tissue-specific expression pattern, similar to Oct-2. Oct-1L differ from ubiquitously expressed Oct-1A in 5'-terminal exon (exon 1L). Analysis of nucleotide sequences from Human Genome Data Bank has located exon 1L about 108 kbp downstream ubiquitously expressed exon 1U. Amino terminus of Oct-1L show extensive similarity to amino terminus of Oct-2. We suppose, that Oct-1L may has a specific role in gene expression in lymphoid tissues and brain.
Asunto(s)
Empalme Alternativo/genética , Proteínas de Unión al ADN/genética , Factores de Transcripción/genética , Proteínas de Unión al ADN/biosíntesis , Perfilación de la Expresión Génica , Factor C1 de la Célula Huésped , Humanos , Células Jurkat , Factor 1 de Transcripción de Unión a Octámeros , Factor 2 de Transcripción de Unión a Octámeros , Especificidad de Órganos , Isoformas de Proteínas/genética , Análisis de Secuencia de ADN , Factores de Transcripción/biosíntesisRESUMEN
The ubiquitous transcription factor Oct-1 is a member of the POU domain family of regulatory proteins. Target genes controlled by Oct-1 include housekeeping genes, e.g. the genes encoding histon H2B or snRNAs, as well as tissue-specific genes, e.g. the genes encoding the light and heavy chains of immunoglobulines, some interleukins, and others. Oct-1 pre-mRNA may be spliced in several ways, resulting in production of several protein isoforms that may differ functionally. The 5'-end of the Oct-1 gene contains two exons-exon 1U and exon 1L that alternatively present in Oct-1 mRNA. We studied regulation of transcription of the Oct-1 gene using reporter gene assays of promoter-luciferase gene-constructs. It was shown that transcription of the Oct-1 gene is regulated by two promoters located upstream of the exon 1U and upstream of the exon 1L. The promoter located upstream of the exon 1U contains G/C-rich sequences and multiple Sp1 sites, while the promoter located upstream of the exon 1L contains A/T-rich motifs and autoregulation-related cis-elements: two octamer sites ATGCAAAT, two octamer related sites and multiple TAAT-core sites. Exons 1U and 1L in the human OTF-1 locus encoding the Oct-1 gene are located at the distance of 108 kbp. In the murine locus otf-1 the distance between exons 1U and 1L is 67 kbp. We suggest that the two promoters can differ functionally.