Odom DT, Zizlsperger N, Gordon DB, Bell GW, Rinaldi NJ, Murray HL, Volkert TL, Schreiber J, Rolfe PA, Gifford DK, Fraenkel E, Bell GI, Young RA
Science. 2004 303 (5662)
· PMCID: PMC3012624
The transcriptional regulatory networks that specify and maintain human tissue diversity are largely uncharted. To gain insight into this circuitry, we used chromatin immunoprecipitation combined with promoter microarrays to identify systematically the genes occupied by the transcriptional regulators HNF1alpha, HNF4alpha, and HNF6, together with RNA polymerase II, in human liver and pancreatic islets. We identified tissue-specific regulatory circuits formed by HNF1alpha, HNF4alpha, and HNF6 with other transcription factors, revealing how these factors function as master regulators of hepatocyte and islet transcription. Our results suggest how misregulation of HNF4alpha can contribute to type 2 diabetes.
MeSH Terms (27)Basic Helix-Loop-Helix Leucine Zipper Transcription Factors Carbohydrate Metabolism Diabetes Mellitus, Type 2 DNA-Binding Proteins Gene Expression Profiling Gene Expression Regulation Genome, Human Gluconeogenesis Hepatocyte Nuclear Factor 1 Hepatocyte Nuclear Factor 1-alpha Hepatocyte Nuclear Factor 1-beta Hepatocyte Nuclear Factor 4 Hepatocyte Nuclear Factor 6 Hepatocytes Homeodomain Proteins Humans Islets of Langerhans Lipid Metabolism Nuclear Proteins Oligonucleotide Array Sequence Analysis Phosphoproteins Precipitin Tests Promoter Regions, Genetic RNA Polymerase II Trans-Activators Transcription, Genetic Transcription Factors