Poungvarin Naravat, Chang Benny, Imamura Minako, Chen Junsheng, Moolsuwan Kanya, Sae-Lee Chanachai, Li Wei, Chan Lawrence
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.
Endocrinology. 2015 Jun;156(6):1982-94. doi: 10.1210/en.2014-1666. Epub 2015 Mar 9.
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.
葡萄糖是一种必需营养素，可直接调节肝脏和脂肪组织中众多基因的表达。碳水化合物反应元件结合蛋白（ChREBP）将作为信号分子的葡萄糖与多种葡萄糖依赖性转录调控途径相联系，特别是与糖酵解和脂肪生成过程相关的基因。在本研究中，我们使用染色质免疫沉淀结合下一代测序技术来鉴定肝脏和白色脂肪组织中特定的ChREBP结合靶点。我们发现了大量的ChREBP结合位点，其中肝脏中有5825个基因、白色脂肪组织中有2418个基因以及两种组织中共有5919个基因。这些靶基因中的大多数参与已知的代谢过程。胰岛素信号传导、黏着连接和癌症相关途径在两种组织中均位列前5大途径。基序分析揭示了一个共有序列CAYGYGnnnnnCRCRTG，该序列为ChREBP结合位点所共有。推测的ChREBP结合序列在参与胰岛素信号通路、胰岛素抵抗和肿瘤发生的基因启动子上富集。
