Journal
SCIENCE
Volume 303, Issue 5662, Pages 1378-1381Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.1089769
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Funding
- NHGRI NIH HHS [R01 HG002668-01, R01 HG002668] Funding Source: Medline
- NIDDK NIH HHS [N01-DK-9-2310] Funding Source: Medline
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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.
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