First Author | Mbikay M | Year | 2002 |
Journal | Brain Res Mol Brain Res | Volume | 102 |
Issue | 1-2 | Pages | 35-47 |
PubMed ID | 12191492 | Mgi Jnum | J:77569 |
Mgi Id | MGI:2182031 | Doi | 10.1016/s0169-328x(02)00180-8 |
Citation | Mbikay M, et al. (2002) Characterization of a repressor element in the promoter region of proprotein convertase 2 (PC2) gene. Brain Res Mol Brain Res 102(1-2):35 |
abstractText | The proprotein convertase PC2 is primarily expressed in neuroendocrine cells where it mediates the proteolytic maturation of prohormones and proneuropeptides. We have identified in the upstream sequence of its gene a conserved domain partially homologous to the repressor element RE1/NRSE found in several genes for neuronal proteins. RE1/NRSE binds the silencing transcription factor REST/NRSF, a nuclear protein primarily found in nonneuronal cells. To determine the functionality of the PC2 gene RE1-like sequence (RE1-lk), we examined by electrophoretic mobility shift assays its ability to attach nuclear factors from PC2-expressing and nonexpressing cells. Specific binding factors were mostly detectable in PC2-non-expressing cells. These factors differ from REST/NRSF, as molar excess of competing RE1/NRSE could not prevent their binding to RE1-lk. Reciprocally, molar excess of RE1-lk could not prevent the binding of RE1/NRSE to the DNA-binding domain of a recombinant REST/NRSF. The presence of RE1-lk in cis reduced the ability of the PC2 promoter and the heterologous phosphoglycerate kinase promoter to drive expression of a green fluorescent protein reporter gene in transiently transfected PC2-nonexpressing cells, but not in PC2-expressing cells. These observations suggest that binding of transcription-silencing factors to the RE1-lk element may contribute to repression of the PC2 gene in nonneuroendocrine cells. |