Understanding the mechanisms controlling beta-cell disallowed genes

Genetics and Genomics

Summary

Understanding how and why certain genes must be turned off in pancreatic beta-cells and how, when they are incorrectly switched on, they can cause diseases like congenital hyperinsulinism.

How are we doing it?

A survey will be conducted of existing and public data on disallowed gene expression and epigenetic states identifying mechanisms of repression. We will collect human fetal pancreatic tissue for functional genomic analysis over the timecourse between 8-21 weeks post conception. Tissue will be subjected to ChIP-seq/CUT&TAG for histone modifications and key transcription factor binding assays. Perform targeted single-molecule footprinting. Laboratory assays in cultured cells will also be conducted.

What happens next?

Using public gene expression datasets to narrow down list of repressed genes to focus on.

Funding

NIHR Exeter BRC

People Involved

Dr Nick Owens and Professor Sarah Flanagan