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Control of Pancreas and Liver Gene Expression by HNF Transcription Factors
Duncan T. Odom,1
Nora Zizlsperger,1,2
D. Benjamin Gordon,1
George W. Bell,1
Nicola J. Rinaldi,1,2
Heather L. Murray,1
Tom L. Volkert,1
Jörg Schreiber,1
P. Alexander Rolfe,3
David K. Gifford,3
Ernest Fraenkel,1
Graeme I. Bell,4
Richard A. Young1,2*
Abstract:
The transcriptional regulatory networks that specify and maintainhuman tissue diversity are largely uncharted. To gain insightinto this circuitry, we used chromatin immunoprecipitation combinedwith promoter microarrays to identify systematically the genesoccupied by the transcriptional regulators HNF1, HNF4, and HNF6,together with RNA polymerase II, in human liver and pancreaticislets. We identified tissue-specific regulatory circuits formedby HNF1, HNF4, and HNF6 with other transcription factors, revealinghow these factors function as master regulators of hepatocyteand islet transcription. Our results suggest how misregulationof HNF4 can contribute to type 2 diabetes.
1 Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA. 2 Department of Biology, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139, USA. 3 MIT Laboratory of Computer Science, 200 Technology Square, Cambridge, MA 02139, USA. 4 Departments of Biochemistry and Molecular Biology, Medicine, and Human Genetics, University of Chicago, Chicago, IL 60637, USA.
* To whom correspondence should be addressed. E-mail: young{at}wi.mit.edu
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|Abstract »|Full Text »|PDF »
Antitumor activity of histone deacetylase inhibitors in non-small cell lung cancer cells: development of a molecular predictive model.
A. Miyanaga, A. Gemma, R. Noro, K. Kataoka, K. Matsuda, M. Nara, T. Okano, M. Seike, A. Yoshimura, A. Kawakami, et al. (2008)
Mol. Cancer Ther.
7, 1923-1930
|Abstract »|Full Text »|PDF »
Common Variants in Maturity-Onset Diabetes of the Young Genes and Future Risk of Type 2 Diabetes.
J. Holmkvist, P. Almgren, V. Lyssenko, C. M. Lindgren, K.-F. Eriksson, B. Isomaa, T. Tuomi, P. Nilsson, and L. Groop (2008)
Diabetes
57, 1738-1744
|Abstract »|Full Text »|PDF »
Persistent Hyperinsulinemic Hypoglycemia and Maturity-Onset Diabetes of the Young Due to Heterozygous HNF4A Mutations.
R. R. Kapoor, J. Locke, K. Colclough, J. Wales, J. J. Conn, A. T. Hattersley, S. Ellard, and K. Hussain (2008)
Diabetes
57, 1659-1663
|Abstract »|Full Text »|PDF »
Growth Hormone Regulation of Insulin-Like Growth Factor-I Gene Expression May Be Mediated by Multiple Distal Signal Transducer and Activator of Transcription 5 Binding Sites.
Evidence of Interaction Between PPARG2 and HNF4A Contributing to Variation in Insulin Sensitivity in Mexican Americans.
M. H. Black, T. E. Fingerlin, H. Allayee, W. Zhang, A. H. Xiang, E. Trigo, J. Hartiala, A. B. Lehtinen, S. M. Haffner, R. N. Bergman, et al. (2008)
Diabetes
57, 1048-1056
|Abstract »|Full Text »|PDF »
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