Transcription Factors ZEB1 and CREB Promote the Transcription of Bovine 5 Gene.

Alpha/beta hydrolase domain 5 (ABHD5) plays a significant role in intracellular lipid metabolism, which is regulated by a complex network of transcription factors. The transcriptional regulation of the 5 gene in cattle and other livestock, however, has not been previously investigated. Investigations in humans and animal models indicate that the transcription factors zinc finger E-box binding homeobox 1 (ZEB1) and cAMP-response element binding protein (CREB) may play important roles in the transcriptional regulation of 5 in cattle. Our comparison of the sequence similarities in the transcription factor binding sites in , , and revealed high homology. Based on the data collected by the Cistrome Data Browser and its visualization window, we found that ZEB1 and CREB have significant ChIP-seq enrichments in the 5'-untranslated region (5' UTR) of the human 5 gene. In bovine adipocytes, we detected ZEB1 and CREB binding sites in the 5 gene. Mutations in the ZEB1 and CREB binding sites significantly reduced the promoter activity ( < 0.05 and  < 0.01, respectively). Moreover, electrophoretic mobility shift assays and chromatin immunoprecipitation (ChIP) assays demonstrated the binding of the transcription factors and , respectively. And overexpression or silencing the expression of the ZEB1 and CREB, respectively, resulted in significant changes to the 5 promoter activity. Collectively, these results indicate that ZEB1 and CREB are important transcription factors that regulate 5 gene expression in bovine adipocytes. They further our understanding of the transcriptional regulation and biological functions of the bovine 5 gene.