Dual promoter structure of ZFP106: regulation by myogenin and nuclear respiratory factor-1.

摘要: The WD40 repeats containing zinc finger protein 106 (ZFP106) is a conserved mammalian of unknown function. However, its cDNA shares an extended region identity with the scr homology domain 3 binding (Sh3bp3) encoding implicated in insulin signaling pathway. Asking, whether Zfp106 and Sh3bp3 are products same gene, we characterized structures transcriptional regulation human homologue, ZFP106. A TATA-less, CpG island associated promoter (P1), was mapped by 5'-RACE to 19 kb upstream ZFP106 translation start site. P1 active throughout development at low levels all adult tissues examined. cis-element proximal showed specific nuclear respiratory factor-1 (NRF-1). Mutagenesis this site transfection dominant-negative NRF-1 both revealed crucial role activation P1. broad tissue expression contrast high level mRNA observed striated muscle. This prompted additional experiments that established second, TATA box-containing (P2) third coding exon. P2 transcripts encode proteins distinct N-terminal sequences, corresponding rare, alternatively spliced transcript. initiated specifically expressed muscle their strongly upregulated during myogenic, but not adipogenic differentiation. By deletion analysis, between nucleotides -296 +96 sufficient for robust responsiveness myogenic response mediated additive effect myogenin three critical E boxes within region. In addition, enhancer family factors contribute basal myogenesis induced activity. situ hybridization mouse embryos confirmed predominant developmental either (brown fat developing brain) or (striated muscle). Our results suggest roles tissue-specific isoforms growth related metabolism provide foundation further studies into function