Genome-Wide Analysis of ChREBP Binding Sites on Male Mouse Liver and White Adipose Chromatin

被引:79
作者
Poungvarin, Naravat [1 ,2 ]
Chang, Benny [1 ]
Imamura, Minako [1 ,3 ]
Chen, Junsheng [4 ]
Moolsuwan, Kanya [2 ,5 ]
Sae-Lee, Chanachai [2 ]
Li, Wei [4 ]
Chan, Lawrence [1 ]
机构
[1] Baylor Coll Med, Dept Med, Houston, TX 77030 USA
[2] Mahidol Univ, Siriraj Hosp, Fac Med, Clin Mol Pathol Lab,Dept Clin Pathol, Bangkok 10700, Thailand
[3] RIKEN Ctr Integrat Med Sci, Lab Endocrinol Metab & Kidney Dis, Yokohama, Kanagawa 2300045, Japan
[4] Baylor Coll Med, Div Biostat, Dan L Duncan Canc Ctr, Houston, TX 77030 USA
[5] Mahidol Univ, Fac Sci, Multidisciplinary Unit, Program Mol Med, Bangkok 10400, Thailand
基金
美国国家卫生研究院;
关键词
CARBOHYDRATE-RESPONSE ELEMENT; PYRUVATE-KINASE GENE; TRANSCRIPTION FACTOR; PROTEIN CHREBP; RAT HEPATOCYTES; MESSENGER-RNA; CA2+ IONS; GLUCOSE; EXPRESSION; PROMOTER;
D O I
10.1210/en.2014-1666
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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.
引用
收藏
页码:1982 / 1994
页数:13
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