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 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.
Atouf
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F
INSERM CJF93-13, Hospital R. Debré, 48 Boulevard Sérurier, 75019 Paris, France.
Czernichow
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P
Scharfmann
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R
D016475:3T3 Cells; D000818:Animals; D002460:Cell Line; D004299:Dopamine beta-Hydroxylase / Q000235:genetics; D017930:Genes, Reporter; D006801:Humans; D007328:Insulin / Q000096:biosynthesis; D007515:Islets of Langerhans / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D009474:Neurons / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics; D012097:Repressor Proteins / Q000378:metabolism*; D015222:Sodium Channels / Q000235:genetics; D014157:Transcription Factors / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D007328:Insulin; D012333:RNA, Messenger; D016194:Receptors, N-Methyl-D-Aspartate; D012097:Repressor Proteins; D015222:Sodium Channels; D014157:Transcription Factors; D004299:Dopamine beta-Hydroxylase