Imperial College London
Alternate

ProfessorJorgeFerrer

Faculty of Medicine, Department of Metabolism, Digestion and Reproduction

Chair in Medicine and Genetics
 
 
 
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Contact

 

+44 (0)20 7594 0968j.ferrer

 
 
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Location

 

535ICTEM buildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@unpublished{de:2018:10.1101/335869,
author = {de, Lichtenberg KH and Funa, N and Nakic, N and Ferrer, J and Zhu, Z and Huangfu, D and Serup, P},
doi = {10.1101/335869},
title = {Genome-Wide Identification of HES1 Target Genes Uncover Novel Roles for HES1 in Pancreatic Development},
url = {http://dx.doi.org/10.1101/335869},
year = {2018}
}
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RIS format (EndNote, RefMan)

TY  - UNPB
AB  - <jats:title>Abstract</jats:title><jats:p>Notch signalling and the downstream effector HES1 is required for multiple pancreatic cell fate choices during development, but the direct target genes remain poorly characterised. Here we identify direct HES1 target genes on a genome-wide scale using ChIP-seq and RNA-seq analyses combined with human embryonic stem cell (hESC) directed differentiation of CRISPR/Cas9-generated<jats:italic>HES1</jats:italic><jats:sup><jats:italic>-/-</jats:italic></jats:sup>mutant hESC lines. We found that HES1 binds to a distinct set of endocrine-specific genes, a set of genes encoding basic Helix-Loop-Helix (bHLH) proteins not normally expressed in the pancreas, genes in the Notch pathway, and the known HES1 target NEUROG3. RNA-seq analysis of wild type,<jats:italic>HES1</jats:italic><jats:sup>-/-</jats:sup>,<jats:italic>NEUROG3</jats:italic><jats:sup>-/-</jats:sup>, and<jats:italic>HES1</jats:italic><jats:sup>-/-</jats:sup><jats:italic>NEUROG</jats:italic>3<jats:sup>-/-</jats:sup>mutant hESC lines allowed us to uncover NEUROG3-independent, direct HES1 target genes. Among the HES1 bound genes that were derepressed in<jats:italic>HES1</jats:italic><jats:sup>-/-</jats:sup><jats:italic>NEUROG3</jats:italic><jats:sup>-/-</jats:sup>cells compared to<jats:italic>NEUROG3</jats:italic><jats:sup>-/-</jats:sup>cells, we found members of the endocrine-specific gene set, the Notch pathway genes<jats:italic>DLL1</jats:italic>,<jats:italic>DLL4</jats:italic>, and<jats:italic>HEY1</jats:italic>, as well as the non-pancreatic bHLH genes<jats:italic>ASCL1</jats:italic>and<jats:italic>ATOH1</jats:italic>. We also found a large number of transcripts specific to the intestinal secretor
AU  - de,Lichtenberg KH
AU  - Funa,N
AU  - Nakic,N
AU  - Ferrer,J
AU  - Zhu,Z
AU  - Huangfu,D
AU  - Serup,P
DO  - 10.1101/335869
PY  - 2018///
TI  - Genome-Wide Identification of HES1 Target Genes Uncover Novel Roles for HES1 in Pancreatic Development
UR  - http://dx.doi.org/10.1101/335869
ER  -
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