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Cx36 is a target of Beta2/NeuroD1, which associates with prenatal differentiation of insulin-producing β cells

Ait-Lounis, Aouatef
Allagnat, Florent
Haefliger, Jacques-Antoine
Published in Journal of Membrane Biology. 2012, vol. 245, no. 5-6, p. 263-73
Collection Open Access - Licence nationale Springer
Abstract The insulin-producing β cells of pancreatic islets are coupled by connexin36 (Cx36) channels. To investigate what controls the expression of this connexin, we have investigated its pattern during mouse pancreas development, and the influence of three transcription factors that are critical for β-cell development and differentiation. We show that (1) the Cx36 gene (Gjd2) is activated early in pancreas development and is markedly induced at the time of the surge of the transcription factors that determine β-cell differentiation; (2) the cognate protein is detected about a week later and is selectively expressed by β cells throughout the prenatal development of mouse pancreas; (3) a 2-kbp fragment of the Gjd2 promoter, which contains three E boxes for the binding of the bHLH factor Beta2/NeuroD1, ensures the expression of Cx36 by β cells; and (4) Beta2/NeuroD1 binds to these E boxes and, in the presence of the E47 ubiquitous cofactor, transactivates the Gjd2 promoter. The data identify Cx36 as a novel early marker of β cells and as a target of Beta2/NeuroD1, which is essential for β-cell development and differentiation.
Keywords AnimalsBasic Helix-Loop-Helix Transcription Factors/genetics/metabolismCell Differentiation/genetics/physiologyCell LineChromatin ImmunoprecipitationComputational BiologyConnexins/metabolismGap Junctions/metabolismHeLa CellsHumansInsulin-Secreting Cells/metabolismIslets of Langerhans/cytology/metabolismMiceMice, Inbred C57BLProtein Binding/geneticsReverse Transcriptase Polymerase Chain Reaction
PMID: 22729650
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Article (Published version) (607 Kb) - public document Free access
Research groups Couplage cellulaire et connexines (136)
Groupe Reith Walter (pathologie et immunologie) (282)
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NLEND NLEND, Rachel et al. Cx36 is a target of Beta2/NeuroD1, which associates with prenatal differentiation of insulin-producing β cells. In: Journal of Membrane Biology, 2012, vol. 245, n° 5-6, p. 263-73. doi: 10.1007/s00232-012-9447-1 https://archive-ouverte.unige.ch/unige:29179

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Deposited on : 2013-08-12

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