The Krüppel-like zinc finger protein GLIS3 transactivates neurogenin 3 for proper fetal pancreatic islet differentiation in mice

Y. Yang, B. H.J. Chang, V. Yechoor, Weiqin Chen, L. Li, M. J. Tsai, L. Chan

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Aims/hypothesis: Mutations in GLIS3, which encodes a Krüppel-like zinc finger transcription factor, were found to underlie sporadic neonatal diabetes. Inactivation of Glis3 by gene targeting in mice was previously shown to lead to neonatal diabetes, but the underlying mechanism remains largely unknown. We aimed to elucidate the mechanism of action of GLIS family zinc finger 3 (GLIS3) in Glis3 -/- mice and to further decipher its action in in-vitro systems. Methods: We created Glis3 -/- mice and monitored the morphological and biochemical phenotype of their pancreatic islets at different stages of embryonic development. We combined these observations with experiments on Glis3 expressed in cultured cells, as well as in in vitro systems in the presence of other reconstituted components. Results: In vivo and in vitro analyses placed Glis3 upstream of Neurog3, the endocrine pancreas lineage-defining transcription factor. We found that GLIS3 binds to specific GLIS3-response elements in the Neurog3 promoter, activating Neurog3 gene transcription both directly, and synergistically with hepatic nuclear factor 6 and forkhead box A2. Conclusions/interpretation: These results indicate that GLIS3 controls fetal islet differentiation via direct transactivation of Neurog3, a perturbation that causes neonatal diabetes in mice.

Original languageEnglish (US)
Pages (from-to)2595-2605
Number of pages11
JournalDiabetologia
Volume54
Issue number10
DOIs
StatePublished - Oct 1 2011

Fingerprint

Zinc Fingers
Islets of Langerhans
Proteins
Transcription Factors
Gene Targeting
Response Elements
varespladib methyl
Transcriptional Activation
Embryonic Development
Cultured Cells
Phenotype
Mutation
Liver
Genes
In Vitro Techniques

Keywords

  • GLIS3
  • Neonatal diabetes
  • Neurog3
  • Pancreatic islet differentiation

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

The Krüppel-like zinc finger protein GLIS3 transactivates neurogenin 3 for proper fetal pancreatic islet differentiation in mice. / Yang, Y.; Chang, B. H.J.; Yechoor, V.; Chen, Weiqin; Li, L.; Tsai, M. J.; Chan, L.

In: Diabetologia, Vol. 54, No. 10, 01.10.2011, p. 2595-2605.

Research output: Contribution to journalArticle

Yang, Y. ; Chang, B. H.J. ; Yechoor, V. ; Chen, Weiqin ; Li, L. ; Tsai, M. J. ; Chan, L. / The Krüppel-like zinc finger protein GLIS3 transactivates neurogenin 3 for proper fetal pancreatic islet differentiation in mice. In: Diabetologia. 2011 ; Vol. 54, No. 10. pp. 2595-2605.
@article{d596cbbdc3284d258bb9b7be8eb18541,
title = "The Kr{\"u}ppel-like zinc finger protein GLIS3 transactivates neurogenin 3 for proper fetal pancreatic islet differentiation in mice",
abstract = "Aims/hypothesis: Mutations in GLIS3, which encodes a Kr{\"u}ppel-like zinc finger transcription factor, were found to underlie sporadic neonatal diabetes. Inactivation of Glis3 by gene targeting in mice was previously shown to lead to neonatal diabetes, but the underlying mechanism remains largely unknown. We aimed to elucidate the mechanism of action of GLIS family zinc finger 3 (GLIS3) in Glis3 -/- mice and to further decipher its action in in-vitro systems. Methods: We created Glis3 -/- mice and monitored the morphological and biochemical phenotype of their pancreatic islets at different stages of embryonic development. We combined these observations with experiments on Glis3 expressed in cultured cells, as well as in in vitro systems in the presence of other reconstituted components. Results: In vivo and in vitro analyses placed Glis3 upstream of Neurog3, the endocrine pancreas lineage-defining transcription factor. We found that GLIS3 binds to specific GLIS3-response elements in the Neurog3 promoter, activating Neurog3 gene transcription both directly, and synergistically with hepatic nuclear factor 6 and forkhead box A2. Conclusions/interpretation: These results indicate that GLIS3 controls fetal islet differentiation via direct transactivation of Neurog3, a perturbation that causes neonatal diabetes in mice.",
keywords = "GLIS3, Neonatal diabetes, Neurog3, Pancreatic islet differentiation",
author = "Y. Yang and Chang, {B. H.J.} and V. Yechoor and Weiqin Chen and L. Li and Tsai, {M. J.} and L. Chan",
year = "2011",
month = "10",
day = "1",
doi = "10.1007/s00125-011-2255-9",
language = "English (US)",
volume = "54",
pages = "2595--2605",
journal = "Diabetologia",
issn = "0012-186X",
publisher = "Springer Verlag",
number = "10",

}

TY - JOUR

T1 - The Krüppel-like zinc finger protein GLIS3 transactivates neurogenin 3 for proper fetal pancreatic islet differentiation in mice

AU - Yang, Y.

AU - Chang, B. H.J.

AU - Yechoor, V.

AU - Chen, Weiqin

AU - Li, L.

AU - Tsai, M. J.

AU - Chan, L.

PY - 2011/10/1

Y1 - 2011/10/1

N2 - Aims/hypothesis: Mutations in GLIS3, which encodes a Krüppel-like zinc finger transcription factor, were found to underlie sporadic neonatal diabetes. Inactivation of Glis3 by gene targeting in mice was previously shown to lead to neonatal diabetes, but the underlying mechanism remains largely unknown. We aimed to elucidate the mechanism of action of GLIS family zinc finger 3 (GLIS3) in Glis3 -/- mice and to further decipher its action in in-vitro systems. Methods: We created Glis3 -/- mice and monitored the morphological and biochemical phenotype of their pancreatic islets at different stages of embryonic development. We combined these observations with experiments on Glis3 expressed in cultured cells, as well as in in vitro systems in the presence of other reconstituted components. Results: In vivo and in vitro analyses placed Glis3 upstream of Neurog3, the endocrine pancreas lineage-defining transcription factor. We found that GLIS3 binds to specific GLIS3-response elements in the Neurog3 promoter, activating Neurog3 gene transcription both directly, and synergistically with hepatic nuclear factor 6 and forkhead box A2. Conclusions/interpretation: These results indicate that GLIS3 controls fetal islet differentiation via direct transactivation of Neurog3, a perturbation that causes neonatal diabetes in mice.

AB - Aims/hypothesis: Mutations in GLIS3, which encodes a Krüppel-like zinc finger transcription factor, were found to underlie sporadic neonatal diabetes. Inactivation of Glis3 by gene targeting in mice was previously shown to lead to neonatal diabetes, but the underlying mechanism remains largely unknown. We aimed to elucidate the mechanism of action of GLIS family zinc finger 3 (GLIS3) in Glis3 -/- mice and to further decipher its action in in-vitro systems. Methods: We created Glis3 -/- mice and monitored the morphological and biochemical phenotype of their pancreatic islets at different stages of embryonic development. We combined these observations with experiments on Glis3 expressed in cultured cells, as well as in in vitro systems in the presence of other reconstituted components. Results: In vivo and in vitro analyses placed Glis3 upstream of Neurog3, the endocrine pancreas lineage-defining transcription factor. We found that GLIS3 binds to specific GLIS3-response elements in the Neurog3 promoter, activating Neurog3 gene transcription both directly, and synergistically with hepatic nuclear factor 6 and forkhead box A2. Conclusions/interpretation: These results indicate that GLIS3 controls fetal islet differentiation via direct transactivation of Neurog3, a perturbation that causes neonatal diabetes in mice.

KW - GLIS3

KW - Neonatal diabetes

KW - Neurog3

KW - Pancreatic islet differentiation

UR - http://www.scopus.com/inward/record.url?scp=80054107636&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=80054107636&partnerID=8YFLogxK

U2 - 10.1007/s00125-011-2255-9

DO - 10.1007/s00125-011-2255-9

M3 - Article

C2 - 21786021

AN - SCOPUS:80054107636

VL - 54

SP - 2595

EP - 2605

JO - Diabetologia

JF - Diabetologia

SN - 0012-186X

IS - 10

ER -