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

Autor: Calderari S; Sorbonne Universities, University Pierre & Marie Curie, University Paris Descartes, Sorbonne Paris Cité, INSERM UMR_S1138, Cordeliers Research Centre, Paris, France., Ria M; The Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom., Gérard C; Sorbonne Universities, University Pierre & Marie Curie, University Paris Descartes, Sorbonne Paris Cité, INSERM UMR_S1138, Cordeliers Research Centre, Paris, France., Nogueira TC; ULB Center for Diabetes Research, Medical Faculty, Université Libre de Bruxelles (ULB), Brussels, Belgium., Villate O; ULB Center for Diabetes Research, Medical Faculty, Université Libre de Bruxelles (ULB), Brussels, Belgium., Collins SC; The Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom., Neil H; FRE3377, Institut de Biologie et de Technologies de Saclay (iBiTec-S), Commissariat à l'Energie Atomique et aux Énergies Alternatives (CEA), Gif-sur-Yvette cedex, France., Gervasi N; INSERM UMR_S839, Institut du Fer à Moulin, Paris, France., Hue C; Sorbonne Universities, University Pierre & Marie Curie, University Paris Descartes, Sorbonne Paris Cité, INSERM UMR_S1138, Cordeliers Research Centre, Paris, France., Suarez-Zamorano N; Sorbonne Universities, University Pierre & Marie Curie, University Paris Descartes, Sorbonne Paris Cité, INSERM UMR_S1138, Cordeliers Research Centre, Paris, France., Prado C; Sorbonne Universities, University Pierre & Marie Curie, University Paris Descartes, Sorbonne Paris Cité, INSERM UMR_S1138, Cordeliers Research Centre, Paris, France., Cnop M; ULB Center for Diabetes Research, Medical Faculty, Université Libre de Bruxelles (ULB), Brussels, Belgium., Bihoreau MT; The Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom., Kaisaki PJ; The Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom., Cazier JB; Centre for Computational Biology, Medical School, University of Birmingham, Birmingham, United Kingdom., Julier C; INSERM UMR-S 958, Faculté de Médecine Paris Diderot, University Paris 7 Denis-Diderot, Paris, Sorbonne Paris Cité, France., Lathrop M; McGill University and Genome Quebec Innovation Centre, 740 Doctor Penfield Avenue, Montreal, QC H3A 0G1, Canada., Werner M; FRE3377, Institut de Biologie et de Technologies de Saclay (iBiTec-S), Commissariat à l'Energie Atomique et aux Énergies Alternatives (CEA), Gif-sur-Yvette cedex, France., Eizirik DL; ULB Center for Diabetes Research, Medical Faculty, Université Libre de Bruxelles (ULB), Brussels, Belgium., Gauguier D; Sorbonne Universities, University Pierre & Marie Curie, University Paris Descartes, Sorbonne Paris Cité, INSERM UMR_S1138, Cordeliers Research Centre, Paris, France; The Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom; McGill University and Genome Quebec Innovation Centre, 740 Doctor Penfield Avenue, Montreal, QC H3A 0G1, Canada. Electronic address: dominique.gauguier@crc.jussieu.fr.
Jazyk: angličtina
Zdroj: Genomics [Genomics] 2018 Mar; Vol. 110 (2), pp. 98-111. Date of Electronic Publication: 2017 Sep 11.
DOI: 10.1016/j.ygeno.2017.09.001
Abstrakt: 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.
(Copyright © 2017 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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