Scientists have generated a comprehensive map of the gene targets regulated by the transcription factors HNF4A and HNF1A in human pancreatic beta cells and liver cells.
Agency for Science, Technology and Research , SingaporeJun 26 2024 Published in the journal Nature Communications, the study revealed common and tissue-specific molecular pathways regulated by HNF4A and HNF1A, two proteins that possess important functions governing the development and function of the pancreas and liver.
The research team, led by Dr Adrian Teo, Senior Principal Investigator at A*STAR's Institute of Molecular and Cell Biology , used the cutting-edge technique of chromatin immunoprecipitation sequencing to map the genomic binding sites of HNF4A and HNF1A in stem cell-derived models of human pancreatic and liver cells, and in primary human islets.
Zooming in on the pancreatic beta cell targets, the scientists shortlisted several high-confidence genes directly bound and regulated by HNF4A, including HAAO and USH1C, which have not been previously characterized in beta cells. They showed that loss of HAAO or USH1C led to impaired glucose-stimulated insulin secretion in human beta cells, indicating that these genes regulate beta cell function.
Gene Transcription Transcription Factors Cell Cell Biology CHIP Chromatin Genes Genetic Immunoprecipitation Insulin Liver Pancreas Research Technology Type 2 Diabetes
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