EXPRESSION OF NEURONAL TRAITS IN PANCREATIC BETA-CELLS - IMPLICATION OF NEURON-RESTRICTIVE SILENCING FACTOR REPRESSOR ELEMENT SILENCING TRANSCRIPTION FACTOR, A NEURON-RESTRICTIVE SILENCER/

Pancreatic beta cells (insulin-producing cells) and neuronal cells sha re a large number of similarities. Here, we investigate whether the sa me mechanisms could control the expression of neuronal genes in both n eurons and insulin-producing cells. For that purpose, we tested the ro le of the transcriptional repressor neuron-restrictive silencing facto r/repressor element silencing transciption factor (NRSF/REST) in the e xpression of a battery of neuronal genes in insulin-producing cells. N RSF/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. Trans ient expression of REST in insulin-producing cell lines is sufficient to silence a reporter gene containing a NRSF/REST binding site, demons trating 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 cel ls.