Expression of Neuronal Traits in Pancreatic Beta Cells

doi:10.1074/jbc.272.3.1929

Expression of Neuronal Traits in Pancreatic Beta Cells

IMPLICATION OF NEURON-RESTRICTIVE SILENCING FACTOR/REPRESSOR ELEMENT SILENCING TRANSCRIPTION FACTOR, A NEURON-RESTRICTIVE SILENCER*

From INSERM CJF93-13, Hospital R. Debré, 48 Boulevard Sérurier, 75019 Paris, France

^‡To whom correspondence should be addressed:
INSERM CJF93-13, Hospital R. Debré, 48 Bd. Sérurier, 75019 Paris, France.
Tel.: 33-1-40034761; Fax: 33-1-40032020; E-mail: scharfma{at}infobiogen.fr

Abstract

Pancreatic beta cells (insulin-producing cells) and neuronal cells share a large number of similarities. Here, we investigate whether the same mechanisms could control the expression of neuronal genes in both neurons and insulin-producing cells. For that purpose, we tested the role of the transcriptional repressor neuron-restrictive silencing factor/repressor element silencing transciption factor (NRSF/REST) in the expression of a battery of neuronal genes in insulin-producing cells. NRSF/REST is a negative regulator of the neuronal fate. It is known to silence neuronal-specific genes in non-neuronal cells. We demonstrate that, as in the case of the neuronal pheochromocytoma cell line PC12, mRNA coding for NRSF/REST is absent from the insulinoma cell line INS-1 and from three other insulin- and glucagon-producing cell lines. NRSF/REST activity is also absent from insulin-producing cell lines. Transient expression of REST in insulin-producing cell lines is sufficient to silence a reporter gene containing a NRSF/REST binding site, demonstrating the role of NRSF/REST in the expression of neuronal markers in insulin-producing cells. Finally, by searching for the expression of NRSF/REST-regulated genes in insulin-producing cells, we increased the list of the genes expressed in both neurons and insulin-producing cells.

Footnotes

↵* This work was supported by grants from the Juvenile Diabetes Foundation and from the Association pour la Recherche Contre le Cancer. The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
↵¹ The abbreviations used are:

NRSF

neuron-restrictive silencing factor

REST

repressor element silencing transciption factor

bp

base pair(s)

RT

reverse transcriptase

PCR

polymerase chain reaction

NMDA

N-methyl-D-aspartate.
↵²F. Atouf, P. Czernichow, and R. Scharfmann, unpublished results.
- Received August 20, 1996.
- Revision received October 7, 1996.