Alternative Promoters and Tissue-Specific Regulation of Mouse oct-1 Gene Transcription

Abstract

The gene encoding mouse transcription factor Oct-1 contains two exons, 1U and 1L, at the 5′ end. Oct-1 mRNA from all tissues contains exon 1U, whereas exon 1L is found only in Oct-1 mRNA from mouse and human lymphoid cells. Upstream of 1U and 1L exons, the respective specific promoters, U and L, are located at a considerable distance from each other (67 kb in the mouse otf-1 locus). These regions differ in their structure. The region upstream from exon 1U contains numerous Sp1 sites, whereas the region upstream from exon 1L contains homeospecific NTAATNN sites and two octa sites ATGCAAAT recognized by transcription factors Oct-1, Oct-2, and by other POU domain-containing proteins. The octa and homeospecific sites promote autoregulation of the oct-1 gene. Transfection of U and L promoter fragments within pGL3 Basic plasmid or pGL3 Enhancer vector into lymphoid NS/0 myeloma cells or 10(1) fibroblasts showed that the L promoter activity was many times higher in the myeloma cells than in fibroblasts. Between the sites of translation and transcription initiation from the L promoter, a nucleotide sequence was identified whose elimination resulted in a significantly higher efficiency of transcription initiation from this promoter. Thus, the oct-1 gene contains at least two alternative promoters: the U promoter apparently provides for the constitutive synthesis of Oct-1 protein, whereas the L promoter manifests tissue specificity, contains octa sites, and appears to be self-regulated.