Hnf1alpha (MODY3) controls tissue-specific transcriptional programs and exerts opposed effects on cell growth in pancreatic islets and liver.

ABSTRACT: Heterozygous HNF1A mutations cause pancreatic-islet beta-cell dysfunction and monogenic diabetes (MODY3). Hnf1alpha is known to regulate numerous hepatic genes, yet knowledge of its function in pancreatic islets is more limited. We now show that Hnf1a deficiency in mice leads to highly tissue-specific changes in the expression of genes involved in key functions of both islets and liver. To gain insights into the mechanisms of tissue-specific Hnf1alpha regulation, we integrated expression studies of Hnf1a-deficient mice with identification of direct Hnf1alpha targets. We demonstrate that Hnf1alpha can bind in a tissue-selective manner to genes that are expressed only in liver or islets. We also show that Hnf1alpha is essential only for the transcription of a minor fraction of its direct-tar

SUBMITTER: Servitja JM 

PROVIDER: S-EPMC2682018 | biostudies-literature | 2009 Jun

REPOSITORIES: biostudies-literature