Genome‐wide Mapping of SREBP‐1 Distribution on Mouse liver‐chromatin in Refeeding Condition by using ChIP‐seq Microarray

Abstract

Lipid homeostasis in vertebrates is regulated by a family of transcription factors designated sterol regulatory element binding proteins (SREBPs) implicated in diabetes and other diet‐related disorders. In order to identify the distribution of the SREBP‐1 when nutritional conditions are changed, mice were subjected to a fasting/refeeding protocol. This leads to a high level of SREBP‐1 protein in the liver which we crosslinked to chromatin prepared from livers of the refed mice. The SREBP‐1‐DNA complexes were isolated and subjected to ChIP‐seq procedure. With 6.7 million sequence reads from the anti‐SREBP‐1 chromatin, we used bioinformatics tools to finally identify 427 peaks of SREBP‐1 enrichment versus IgG. We found that SREBP‐1 occupied not only many well characterized SREBP‐1 target genes previously identified but several others putative target genes that are involved in diverse biological pathways, including novel targets with roles in lipid and carbohydrate metabolism. Using the sequences from the peaks, we also identified a preferred SREBP‐1 DNA‐binding motif that was present in 30% of the identified binding sites. This motif ACTACANNTCCC closely matches the consensus SRE site proposed by our lab previously. Our report should be useful for understanding to maintain metabolic homeostasis in response to shifting nutritional fluctuations.