Genome-wide analysis of SREBP-1 binding in mouse liver chromatin reveals a preference for promoter proximal binding to a new motif

摘要: Lipid homeostasis in vertebrates is regulated by 3 sterol regulatory element binding protein (SREBP) isoforms. Here, we identify targets of SREBP-1 mammalian liver using chromatin immunoprecipitation–high-throughput DNA sequencing. Antisera to were used with from mice fed a high-carbohydrate diet after fast, which leads superinduction hepatic SREBP-1c expression. SREBP-1–DNA complexes subjected massive parallel sequencing the Illumina Genome Analyzer II, resulting 5.7 million sequence reads. Mapping these reads mouse reference genome identified 426 peaks vs. control antibody. These show striking enrichment proximal promoter regions, 52% located within 1 kb upstream transcription start site. A previously undescribed motif (5′-ACTACANNTCCC-3′) was present 76% total peaks, and that it functional response element. Our analysis also reveals an Sp1 consensus site as “coregulatory” 50% consistent previous studies. bound not only many well-characterized target genes but several other unknown lipid carbohydrate metabolism well putative diverse biological pathways.