Genome-Wide Analysis of ChREBP Binding Sites on Male Mouse Liver and White Adipose Chromatin.
Glucose is an essential nutrient that directly regulates the expression of numerous genes in liver and adipose tissue. The carbohydrate response element-binding protein (ChREBP) links glucose as a signaling molecule to multiple glucose-dependent transcriptional regulatory pathways, particularly genes involved in glycolytic and lipogenic processes. In this study, we used chromatin immunoprecipitation followed by next-generation sequencing to identify specific ChREBP binding targets in liver and white adipose tissue. We found a large number of ChREBP binding sites, which are attributable to 5825 genes in the liver, 2418 genes in white adipose tissue, and 5919 genes in both tissues. The majority of these target genes were involved in known metabolic processes. Pathways in insulin signaling, the adherens junction, and cancers were among the top 5 pathways in both tissues. Motif analysis revealed a consensus sequence CAYGYGnnnnnCRCRTG that was commonly shared by ChREBP binding sites. Putative ChREBP binding sequences were enriched on promoters of genes involved in insulin signaling pathway, insulin resistance, and tumorigenesis.
Department of Medicine (N.P., B.C., M.I., L.C.), Baylor College of Medicine, Houston, Texas 77030; Clinical Molecular Pathology Laboratory (N.P., K.M., C.S.-L.), Department of Clinical Pathology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand; Laboratory for Endocrinology, Metabolism and Kidney Diseases (M.I.) RIKEN Center for Integrative Medical Sciences, Yokohama, Japan 230-0045; Division of Biostatistics (J.C., W.L.), Dan L. Duncan Cancer Center and Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030; and Molecular Medicine Program (K.M.), Multidisciplinary Unit, Faculty of Science, Mahidol University, Bangkok, Thailand.
Naravat
N
Poungvarin
Benny
B
Chang
Minako
M
Imamura
Junsheng
J
Chen
Kanya
K
Moolsuwan
Chanachai
C
Sae-Lee
Wei
W
Li
Lawrence
L
Chan
D052436:Adipose Tissue, White / Q000378:metabolism*; D000818:Animals; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D001665:Binding Sites; D002843:Chromatin / Q000378:metabolism*; D047369:Chromatin Immunoprecipitation; D055106:Genome-Wide Association Study; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009687:Nuclear Proteins / Q000378:metabolism*; D011485:Protein Binding; D014157:Transcription Factors / Q000378:metabolism*
D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D002843:Chromatin; C506001:Mlxipl protein, mouse; D009687:Nuclear Proteins; D014157:Transcription Factors