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

Young Kyo Seo, Kim Chong Hansook, Aniello M. Infante, Seung Soon Im, Xiaohui Xie, Timothy F. Osborne

Research output: Contribution to journalArticlepeer-review

Abstract

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

Original languageEnglish (US)
Pages (from-to)13765-13769
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume106
Issue number33
DOIs
StatePublished - Aug 18 2009

Keywords

  • Chip-seq
  • Fasting/refeeding
  • Kolmogorov-Smirnov test
  • Sp1

ASJC Scopus subject areas

  • General

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