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Hepatocyte nuclear factor 1 coordinates multiple processes in a model of intestinal epithelial cell function.

Rui Yang1, Jenny L Kerschner1, Ann Harris2

  • 1Human Molecular Genetics Program, Lurie Children's Research Center, Chicago, IL 60614, USA; Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.

Biochimica Et Biophysica Acta
|February 9, 2016
PubMed
Summary

Hepatocyte nuclear factor 1 (HNF1) transcription factors regulate intestinal epithelial cell function. HNF1 directly impacts gene expression and interacts with other key intestinal transcription factors, influencing cell properties and responses.

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Area of Science:

  • Molecular biology
  • Genetics
  • Gastroenterology

Background:

  • Mutations in hepatocyte nuclear factor 1 (HNF1α/β) transcription factors are linked to diabetes.
  • HNF1 factors are crucial for gene regulation in the liver, pancreas, and kidney.
  • HNF1 also plays a significant role in the biology of other tissues, including the intestine.

Purpose of the Study:

  • To investigate the transcriptional network regulated by HNF1 in intestinal epithelial cells.
  • To identify direct HNF1 targets and understand their role in intestinal cell function.

Main Methods:

  • Chromatin immunoprecipitation followed by direct sequencing (ChIP-seq) to map HNF1 binding sites genome-wide.
  • Validation of HNF1 targets using ChIP assays and siRNA-mediated depletion.
  • RT-qPCR to confirm gene expression changes.
  • Gene ontology analysis to identify enriched biological processes.

Main Results:

  • Identified genome-wide HNF1 binding sites in the Caco2 intestinal epithelial cell line.
  • HNF1 targets are involved in cell membrane properties, hormone response, and biosynthesis.
  • Significant overlap of HNF1 binding sites with other intestinal transcription factors (HNF4A, CDX2, FOXA2).
  • HNF1 depletion altered FOXA2 and CDX2 levels, indicating network coordination.

Conclusions:

  • HNF1 is a key regulator of intestinal epithelial cell function.
  • HNF1 directly influences gene expression and interacts with other transcription factors in the intestine.
  • These interactions highlight a coordinated transcriptional network governing intestinal biology.