distinct and histone-specific modifications mediate positive versus negative transcriptional regulation of tshα promoter不同和histone-specific修改调解正面与负面tshα启动子的转录调控.pdfVIP

Distinct and Histone-Specific Modifications Mediate Positive versus Negative Transcriptional Regulation of TSHa Promoter 1 3 4 4 1,2 Dongqing Wang , Xianmin Xia , Roy E. Weiss , Samuel Refetoff , Paul M. Yen * 1 Endocrinology Division, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America, 2 Laboratory of Hormonal Regulation, Cardiovascular and Metabolic Disease Program, Duke-National University of Singapore Graduate Medical School, Singapore, Singapore, 3 DJ Biotech, Changzhou, China, 4 Departments of Medicine and Pediatrics, University of Chicago, Chicago, Illinois, United States of America Abstract Background: Hormonally-regulated histone modifications that govern positive versus negative transcription of target genes are poorly characterized despite their importance for normal and pathological endocrine function. There have been only a few studies examining chromatin modifications on target gene promoters by nuclear hormone receptors. Moreover, these studies have focused on positively-regulated target genes. TSHa, a heterodimer partner for thyrotropin (TSH), is secreted by the pituitary gland. T3 negatively regulates TSHa gene expression via thyroid hormone receptors (TRs) which belong to the nuclear hormone receptor superfamily, whereas thyrotropin releasing hormone (TRH) positively regulates via the TRH receptor, a G protein-coupled receptor. Methodology/Principal Findings: We studied regulation of the TSHa gene by cAMP and T3 using chromatin immunoprecipitation (ChIP) assays in stably-transfected rat pituitary cells containing the human TSHa promoter. Interestingly, cAM