Regulation of a Mammalian Gene Bearing a CpG Island Promoter and a Distal Enhancer

• Eukaryotic genes are controlled primarily by activators
• Nucleosomes at the enhancer form less avidly than at the promoter in the silent gene
• Nucleosome avidity is determined by the GC content of underlying sequences
• Active enhancer replaces a promoter nucleosome with the transcriptional machinery

SummaryA quantitative nucleosome occupancy assay revealed rules for nucleosome disposition in yeast and showed how disposition affects regulation of the GAL genes. Here, we show how those findings apply to the control of Kit, a mammalian gene. The Kit promoter lies in a CpG island, and its enhancer (active in mast cells) lies some 150 kb upstream. Nucleosomes form with especially high avidities at the Kit promoter, a reaction that, we surmise, ensures extremely low basal expression. In mast cells, transcriptional activators displace nucleosomes that are less tightly formed at the Kit enhancer. In turn, the active enhancer replaces a single Kit promoter nucleosome with the transcriptional machinery, thereby inducing transcription over 1,000-fold. As at the yeast GAL genes, the inhibitory effects of nucleosomes facilitate high factors of induction by mammalian activators working in the absence of specific repressors.

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