Genetic evidence that HNF-1α–dependent transcriptional control of HNF-4α is essential for human pancreatic β cell function

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Profound defects in pancreatic -cell function in mice with combined heterozygous mutations in Pdx-1, Hnf-1 , and Hnf-3

Defects in pancreatic -cell function contribute to the development of type 2 diabetes, a polygenic disease that is characterized by insulin resistance and compromised insulin secretion. Hepatocyte nuclear factors (HNFs) -1 , -3 , -4 , and Pdx-1 contribute in the complex transcriptional circuits within the pancreas that are involved in -cell development and function. In mice, a heterozygous muta...

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Functional Targets of the Monogenic Diabetes Transcription Factors HNF-1α and HNF-4α Are Highly Conserved Between Mice and Humans

OBJECTIVE The evolutionary conservation of transcriptional mechanisms has been widely exploited to understand human biology and disease. Recent findings, however, unexpectedly showed that the transcriptional regulators hepatocyte nuclear factor (HNF)-1alpha and -4alpha rarely bind to the same genes in mice and humans, leading to the proposal that tissue-specific transcriptional regulation has u...

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Islet-1 Is Essential for Pancreatic β-Cell Function

Islet-1 (Isl-1) is essential for the survival and ensuing differentiation of pancreatic endocrine progenitors. Isl-1 remains expressed in all adult pancreatic endocrine lineages; however, its specific function in the postnatal pancreas is unclear. Here we determine whether Isl-1 plays a distinct role in the postnatal β-cell by performing physiological and morphometric analyses of a tamoxifen-in...

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The different tissue transcription patterns of genes for HNF-1, C/EBP, HNF-3, and HNF-4, protein factors that govern liver-specific transcription.

The transcription factors that act in hepatocyte-specific gene expression include proteins that are present mainly in liver cells (HNF-1/LFB1, C/EBP, HNF-3, HNF-4) (HNF, hepatocyte nuclear factor; C/EBP, rat enhancer binding protein) and proteins that are widely distributed (AP-1, NF-1, NF-Y/ACF). We show here that the genes encoding each of these liver-enriched factors exhibit different patter...

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ژورنال

عنوان ژورنال: Journal of Clinical Investigation

سال: 2002

ISSN: 0021-9738

DOI: 10.1172/jci200215085