Two CACGTG Motifs with Proper Spacing Dictate the Carbohydrate Regulation of Hepatic Gene Transcription

摘要: Regulatory sequences involved in the transcriptional induction of rat S14 gene response to increased glucose metabolism hepatocyte were investigated and compared with those liver-type pyruvate kinase (L-PK) gene. The carbohydrate element (ChoRE) was found consist two motifs related consensus binding site for c-myc family transcription factors, CACGTG. These are separated by five base pairs, a similar arrangement that L-PK ChoRE. In its natural context, ChoRE requires novel accessory factor support full glucose. This factor, as well hepatic nuclear factor-4, both capable enhance regulation. need an supporting can be overcome ways. First, multimers ChoREs either or genes function independently response. Second, mutations create perfect match CACGTG motif at each locus no longer require site. spacing motifs, but not nature bases within spacer, critical control. observations suggest responsive binds highly specific spatial orientation confer metabolism.