Negative transcriptional regulation of the chicken Na+/K+-ATPase α1-subunit genea

摘要

Although the Na+/K+-ATPase a 1-subunit gene is ubiquitously expressed in vertebrates, its level of expression varies among tissue and cell types. In spite of similar mRNA distribution in tissues of mammals and birds, the 5'-flanking regions of u I-subunit genes exhibit remarkable diversity; i.e., the core promoter activity of the TATA-less chicken al gene strongly depends upon multiple Spl-based regulation (six Spl sites), whereas the promoter activity of the TATA-like rat (xl-subunit gene relies on the two Spl and additional positive regulatory factors. Further analysis of the regulatory regions of the Na'/K+-ATPase a 1-subunit genes revealed that the vertebrate al-subunit genes may share common inhibitory mechanisms For subtle transcriptional regulation; the core promoter activities can be either enhanced or repressed depending on the availability of inhibitory factors. Two potential candidates for such inhibitory elements in both avian and mammalian Na '/K '-ATPase al-subunit genes are (1) a newly identified element, GCCCTC, and (2) a GCF-binding sequence, NN[G/e]CG[G/c][G/c][G/c]CN, or its reverse complement. Gel retardation assays using the inhibitory region of the chicken gene and crude nuclear extracts from tissue-cultured chicken and mouse cells showed the existence of a set of proteins that bind to this region. The amounts of individual regulatory proteins in different cell types seem to vary, resulting in differential formation of DNA/protein complexes in different cell types. Thus, the regulation of Na+/K+-ATPase al-subunit gene expression under different cellular environment as well as in different cell types can be achieved by a shared mechanism; modulation of the ratio of the abundance of individual inhibitory factors.