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Description

RE1-silencing transcription factor (also known as REST, Neural-restrictive silencer factor, X2 box repressor) is encoded by the REST (also known as NRSF, XBR) gene (Gene ID: 422623) in chicken. REST is a transcriptional repressor that acts by binding a DNA sequence element called the neuron-restrictive silencer element (NRSE). It is ubiquitously expressed, and higher expression is found in the tissues of the lymphocytic compartment, including spleen, thymus, peripheral blood lymphocytes, and ovary. It is also found in undifferentiated neuronal progenitor cells and it is believed that it acts as a master negative regular of neurogenesis. REST is also required to repress endogenous neuronal target genes in non-neuronal tissues, and also to repress these genes in neural precursors. Expression of REST is reported to be cell cycle-dependent with reduced levels in the G2 phase. REST restricts the expression of neuronal genes by associating with two distinct corepressors, SIN3A and RCOR1, which in turn recruit histone deacetylase to the promoters of REST-regulated genes. REST also mediates repression by recruiting the BHC complex at RE1/NRSE sites, which acts by deacetylating and demethylating specific sites on histones and acting as a chromatin modifier. REST is shown to contain nine zinc finger domains, but a C-terminally truncated form is also produced by alternative splicing. Mutations in human REST gene can lead to Wilms tumors, a pediatric malignancy of the kidney that occurs due to uncontrolled multiplication of renal stem, stromal, and epithelial cells. ((Ref.: Chen, ZF., et al. (1998). Nat. Genet. 20(2), 136-142).