Molecular genetics of the transcription factor GLIS3 identifies its dual function in beta cells and neurons

Sophie Calderari; Massimiliano Ria; Christelle Gérard; Tatiane C. Nogueira; Olatz Villate; Stephan C. Collins; Helen Neil; Nicolas Gervasi; Christophe Hue; Nicolas Suarez-zamorano; Cécilia Prado; Miriam Cnop; Marie-thérèse Bihoreau; Pamela J. Kaisaki; Jean-baptiste Cazier; Cécile Julier; Mark Lathrop; Michel Werner; Decio L. Eizirik; Dominique Gauguier

doi:10.1016/j.ygeno.2017.09.001

Molecular genetics of the transcription factor GLIS3 identifies its dual function in beta cells and neurons

Sophie Calderari
, Massimiliano Ria
, Christelle Gérard
, Tatiane C. Nogueira
, Olatz Villate
, Stephan C. Collins
, Helen Neil
, Nicolas Gervasi
, Christophe Hue
, Nicolas Suarez-zamorano
, Cécilia Prado
, Miriam Cnop
, Marie-thérèse Bihoreau
, Pamela J. Kaisaki
, Jean-baptiste Cazier
, Cécile Julier
, Mark Lathrop
, Michel Werner
, Decio L. Eizirik
, Dominique Gauguier

Cancer and Genomic Sciences

Research output: Contribution to journal › Article › peer-review

13 Citations (Scopus)

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Abstract

The GLIS family zinc finger 3 isoform (GLIS3) is a risk gene for Type 1 and Type 2 diabetes, glaucoma and Alzheimer's disease endophenotype. We identified GLIS3 binding sites in insulin secreting cells (INS1) (FDR q < 0.05; enrichment range 1.40–9.11 fold) sharing the motif wrGTTCCCArTAGs, which were enriched in genes involved in neuronal function and autophagy and in risk genes for metabolic and neuro-behavioural diseases. We confirmed experimentally Glis3-mediated regulation of the expression of genes involved in autophagy and neuron function in INS1 and neuronal PC12 cells. Naturally-occurring coding polymorphisms in Glis3 in the Goto-Kakizaki rat model of type 2 diabetes were associated with increased insulin production in vitro and in vivo, suggestive alteration of autophagy in PC12 and INS1 and abnormal neurogenesis in hippocampus neurons. Our results support biological pleiotropy of GLIS3 in pathologies affecting β-cells and neurons and underline the existence of trans‑nosology pathways in diabetes and its co-morbidities.

Original language	English
Pages (from-to)	98-111
Number of pages	14
Journal	Genomics
Volume	110
Issue number	2
Early online date	11 Sept 2017
DOIs	https://doi.org/10.1016/j.ygeno.2017.09.001
Publication status	Published - 2018

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Alzheimer's disease
ChIP sequencing
diabetes mellitus
Goto-Kakizaki rat
quantitative trait locus
single nucleotide polymorphism

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Calderari, S., Ria, M., Gérard, C., Nogueira, T. C., Villate, O., Collins, S. C., Neil, H., Gervasi, N., Hue, C., Suarez-zamorano, N., Prado, C., Cnop, M., Bihoreau, M., Kaisaki, P. J., Cazier, J., Julier, C., Lathrop, M., Werner, M., Eizirik, D. L., & Gauguier, D. (2018). Molecular genetics of the transcription factor GLIS3 identifies its dual function in beta cells and neurons. Genomics, 110(2), 98-111. https://doi.org/10.1016/j.ygeno.2017.09.001

@article{f1dec089b3d14dafb58103bac4da4f03,

title = "Molecular genetics of the transcription factor GLIS3 identifies its dual function in beta cells and neurons",

abstract = "The GLIS family zinc finger 3 isoform (GLIS3) is a risk gene for Type 1 and Type 2 diabetes, glaucoma and Alzheimer's disease endophenotype. We identified GLIS3 binding sites in insulin secreting cells (INS1) (FDR q < 0.05; enrichment range 1.40–9.11 fold) sharing the motif wrGTTCCCArTAGs, which were enriched in genes involved in neuronal function and autophagy and in risk genes for metabolic and neuro-behavioural diseases. We confirmed experimentally Glis3-mediated regulation of the expression of genes involved in autophagy and neuron function in INS1 and neuronal PC12 cells. Naturally-occurring coding polymorphisms in Glis3 in the Goto-Kakizaki rat model of type 2 diabetes were associated with increased insulin production in vitro and in vivo, suggestive alteration of autophagy in PC12 and INS1 and abnormal neurogenesis in hippocampus neurons. Our results support biological pleiotropy of GLIS3 in pathologies affecting β-cells and neurons and underline the existence of trans‑nosology pathways in diabetes and its co-morbidities.",

keywords = "Alzheimer's disease , ChIP sequencing , diabetes mellitus , Goto-Kakizaki rat , quantitative trait locus , single nucleotide polymorphism",

author = "Sophie Calderari and Massimiliano Ria and Christelle G{\'e}rard and Nogueira, \{Tatiane C.\} and Olatz Villate and Collins, \{Stephan C.\} and Helen Neil and Nicolas Gervasi and Christophe Hue and Nicolas Suarez-zamorano and C{\'e}cilia Prado and Miriam Cnop and Marie-th{\'e}r{\`e}se Bihoreau and Kaisaki, \{Pamela J.\} and Jean-baptiste Cazier and C{\'e}cile Julier and Mark Lathrop and Michel Werner and Eizirik, \{Decio L.\} and Dominique Gauguier",

year = "2018",

doi = "10.1016/j.ygeno.2017.09.001",

language = "English",

volume = "110",

pages = "98--111",

journal = "Genomics",

issn = "0888-7543",

publisher = "Elsevier",

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}

Calderari, S, Ria, M, Gérard, C, Nogueira, TC, Villate, O, Collins, SC, Neil, H, Gervasi, N, Hue, C, Suarez-zamorano, N, Prado, C, Cnop, M, Bihoreau, M, Kaisaki, PJ, Cazier, J, Julier, C, Lathrop, M, Werner, M, Eizirik, DL & Gauguier, D 2018, 'Molecular genetics of the transcription factor GLIS3 identifies its dual function in beta cells and neurons', Genomics, vol. 110, no. 2, pp. 98-111. https://doi.org/10.1016/j.ygeno.2017.09.001

TY - JOUR

T1 - Molecular genetics of the transcription factor GLIS3 identifies its dual function in beta cells and neurons

AU - Calderari, Sophie

AU - Ria, Massimiliano

AU - Gérard, Christelle

AU - Nogueira, Tatiane C.

AU - Villate, Olatz

AU - Collins, Stephan C.

AU - Neil, Helen

AU - Gervasi, Nicolas

AU - Hue, Christophe

AU - Suarez-zamorano, Nicolas

AU - Prado, Cécilia

AU - Cnop, Miriam

AU - Bihoreau, Marie-thérèse

AU - Kaisaki, Pamela J.

AU - Cazier, Jean-baptiste

AU - Julier, Cécile

AU - Lathrop, Mark

AU - Werner, Michel

AU - Eizirik, Decio L.

AU - Gauguier, Dominique

PY - 2018

Y1 - 2018

N2 - The GLIS family zinc finger 3 isoform (GLIS3) is a risk gene for Type 1 and Type 2 diabetes, glaucoma and Alzheimer's disease endophenotype. We identified GLIS3 binding sites in insulin secreting cells (INS1) (FDR q < 0.05; enrichment range 1.40–9.11 fold) sharing the motif wrGTTCCCArTAGs, which were enriched in genes involved in neuronal function and autophagy and in risk genes for metabolic and neuro-behavioural diseases. We confirmed experimentally Glis3-mediated regulation of the expression of genes involved in autophagy and neuron function in INS1 and neuronal PC12 cells. Naturally-occurring coding polymorphisms in Glis3 in the Goto-Kakizaki rat model of type 2 diabetes were associated with increased insulin production in vitro and in vivo, suggestive alteration of autophagy in PC12 and INS1 and abnormal neurogenesis in hippocampus neurons. Our results support biological pleiotropy of GLIS3 in pathologies affecting β-cells and neurons and underline the existence of trans‑nosology pathways in diabetes and its co-morbidities.

AB - The GLIS family zinc finger 3 isoform (GLIS3) is a risk gene for Type 1 and Type 2 diabetes, glaucoma and Alzheimer's disease endophenotype. We identified GLIS3 binding sites in insulin secreting cells (INS1) (FDR q < 0.05; enrichment range 1.40–9.11 fold) sharing the motif wrGTTCCCArTAGs, which were enriched in genes involved in neuronal function and autophagy and in risk genes for metabolic and neuro-behavioural diseases. We confirmed experimentally Glis3-mediated regulation of the expression of genes involved in autophagy and neuron function in INS1 and neuronal PC12 cells. Naturally-occurring coding polymorphisms in Glis3 in the Goto-Kakizaki rat model of type 2 diabetes were associated with increased insulin production in vitro and in vivo, suggestive alteration of autophagy in PC12 and INS1 and abnormal neurogenesis in hippocampus neurons. Our results support biological pleiotropy of GLIS3 in pathologies affecting β-cells and neurons and underline the existence of trans‑nosology pathways in diabetes and its co-morbidities.

KW - Alzheimer's disease

KW - ChIP sequencing

KW - diabetes mellitus

KW - Goto-Kakizaki rat

KW - quantitative trait locus

KW - single nucleotide polymorphism

UR - https://www.scopus.com/pages/publications/85029499517

U2 - 10.1016/j.ygeno.2017.09.001

DO - 10.1016/j.ygeno.2017.09.001

M3 - Article

SN - 0888-7543

VL - 110

SP - 98

EP - 111

JO - Genomics

JF - Genomics

IS - 2

ER -

Molecular genetics of the transcription factor GLIS3 identifies its dual function in beta cells and neurons

Abstract

UN SDGs

Keywords

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