Imperial College London
Alternate

ProfessorGuyRutter

Faculty of Medicine, Department of Medicine

Visiting Professor
 
 
 
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Contact

 

+44 (0)20 7594 3340g.rutter Website

 
 
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Location

 

ICTEM buildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Hu:2021:10.1016/j.celrep.2021.108881,
author = {Hu, M and Cebola, I and Carrat, G and Jiang, S and Nawaz, S and Khamis, A and Canouil, M and Froguel, P and Schulte, A and Solimena, M and Ibberson, M and Marchetti, P and Cardenas-Diaz, FL and Gadue, PJ and Hastoy, B and Almeida-Souza, L and McMahon, H and Rutter, GA},
doi = {10.1016/j.celrep.2021.108881},
journal = {Cell Research},
pages = {1--1},
title = {Chromatin 3D interaction analysis of the STARD10 locus unveils FCHSD2 as a regulator of insulin secretion.},
url = {http://dx.doi.org/10.1016/j.celrep.2021.108881},
volume = {34},
year = {2021}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Using chromatin conformation capture, we show that an enhancer cluster in the STARD10 type 2 diabetes (T2D) locus forms a defined 3-dimensional (3D) chromatin domain. A 4.1-kb region within this locus, carrying 5 T2D-associated variants, physically interacts with CTCF-binding regions and with an enhancer possessing strong transcriptional activity. Analysis of human islet 3D chromatin interaction maps identifies the FCHSD2 gene as an additional target of the enhancer cluster. CRISPR-Cas9-mediated deletion of the variant region, or of the associated enhancer, from human pancreas-derived EndoC-βH1 cells impairs glucose-stimulated insulin secretion. Expression of both STARD10 and FCHSD2 is reduced in cells harboring CRISPR deletions, and lower expression of STARD10 and FCHSD2 is associated, the latter nominally, with the possession of risk variant alleles in human islets. Finally, CRISPR-Cas9-mediated loss of STARD10 or FCHSD2, but not ARAP1, impairs regulated insulin secretion. Thus, multiple genes at the STARD10 locus influence β cell function.
AU  - Hu,M
AU  - Cebola,I
AU  - Carrat,G
AU  - Jiang,S
AU  - Nawaz,S
AU  - Khamis,A
AU  - Canouil,M
AU  - Froguel,P
AU  - Schulte,A
AU  - Solimena,M
AU  - Ibberson,M
AU  - Marchetti,P
AU  - Cardenas-Diaz,FL
AU  - Gadue,PJ
AU  - Hastoy,B
AU  - Almeida-Souza,L
AU  - McMahon,H
AU  - Rutter,GA
DO  - 10.1016/j.celrep.2021.108881
EP  - 1
PY  - 2021///
SN  - 1001-0602
SP  - 1
TI  - Chromatin 3D interaction analysis of the STARD10 locus unveils FCHSD2 as a regulator of insulin secretion.
T2  - Cell Research
UR  - http://dx.doi.org/10.1016/j.celrep.2021.108881
UR  - https://www.ncbi.nlm.nih.gov/pubmed/33730570
UR  - https://www.sciencedirect.com/science/article/pii/S2211124721001959?via%3Dihub
UR  - http://hdl.handle.net/10044/1/86586
VL  - 34
ER  -
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