Regulation of oct-1 gene transcription is different in lymphoid and non-lymphoid cells.

ABSTRACT

Transcription factor Oct-1 is expressed in all eukaryotic cells acting as a positive or negative regulator of gene transcription and DNA replication. Being a ubiquitous nuclear protein, Oct-1 also takes part in the regulation of tissue-specific gene expression. In this paper, we have found that human oct-1 gene is regulated by two promoters, located in OTF-1 locus upstream of 1U and 1L exons, respectively. The DNA region preceding U exon has a pattern typical of the constitutive gene promoters. The 5'-region upstream of 1L-exon is AT-rich, contains no TATA box, but has two octamer sequences targeted by Oct-1 and Oct-2 proteins. Analysis of promoter activity is carried out by transfection of recombinant plasmids in non-lymphoid HEK293 and lymphoid Raji cells. In non-lymphoid cells, efficiency of transcription from the 1U promoter several times exceeded that from the 1L promoter. The 1U promoter activity is little increased in the presence of an external enhancer. A different expression pattern was observed if the same constructs were transfected into lymphoid Raji cells. In this case, the level of transcription from the 1L promoter (the L-2 fragment, containing a proximal octamer site) in the presence of the enhancer was significantly higher than that of any fragments containing 1U promoter. It was shown that distal regions of both 1U and 1L were capable of silencing activity. In Raji cells, the enhancer completely overcomes the activity of U silencer, but only partly overcomes that of L silencer. Our data on tissue-specific features of 1L promoter and interaction of both oct-1 promoters with enhancer and silencers in different cell types point to a fine tissue-specific regulation of the oct-1 gene expression, especially in lymphoid cells.