REST
REST (RE1-silencing transcription factor, also known as NRSF, XBR and DFNA27) is a Kruppel-type zinc finger transcription factor that represses neuronal genes by binding the neuron-restrictive silencer element. It was first identified as a repressor of neuronal genes in non-neuronal tissues. Browse Assay Genie's current range of REST research reagents below, or read on for the biology behind the target.
REST acts as a transcriptional repressor. It binds a DNA sequence called the neuron-restrictive silencer element (NRSE) and represses transcription of genes that carry it. The protein was initially identified as a repressor of neuronal genes in non-neuronal tissues, which gave rise to the name neuron-restrictive silencer factor. It is also found in undifferentiated neuronal progenitor cells, and it is thought that it may act as a master negative regulator of neurogenesis.
The REST gene encodes a member of the Kruppel-type zinc finger transcription factor family, classed by HGNC in the C2H2-type zinc finger group. UniProt records localisation in the nucleus and the cytoplasm. Alternatively spliced transcript variants have been described, and these matter functionally. A shorter isoform binds the 3' region of the NRSE with lower affinity than full-length isoform 1 and shows weaker repressor activity. One study suggests it may counter isoform 1 by binding to it and preventing its binding to the NRSE, leading to derepression of target genes. Another study found no role for it in repressor activity of an NRSE-containing reporter construct, or in inhibiting isoform 1.
Splicing control of REST has a physiological role in hearing. SRRM4-dependent alternative splicing inactivates REST post-transcriptionally into isoform 3. This is required in mechanosensory hair cells of the inner ear for derepression of neuronal genes and for hearing. This link explains the earlier designation DFNA27, from the HGNC name 'deafness, autosomal dominant 27'. NCBI Gene also notes that, depending on cellular context, REST can act as either an oncogene or a tumour suppressor.
REST is thought to act as a master negative regulator of neurogenesis and is found in undifferentiated neuronal progenitor cells.
REST binds the neuron-restrictive silencer element to repress target genes, making it a model for silencer-mediated gene regulation.
Depending on cellular context, REST can act as an oncogene or a tumour suppressor, so its role is studied in different tumour settings.
SRRM4-dependent splicing to isoform 3 inactivates REST in hair cells, allowing neuronal gene derepression needed for hearing.
REST is a transcriptional repressor that binds the neuron-restrictive silencer element to repress neuronal genes in non-neuronal tissues. It is also present in undifferentiated neuronal progenitor cells and is thought to act as a master negative regulator of neurogenesis. Check the datasheet of any product for its validated reactivity.
REST is also known as NRSF, XBR and DFNA27; the previous HGNC name was deafness, autosomal dominant 27. Alternatively spliced variants exist. Isoform 1 is the full-length repressor, while shorter forms such as isoform 3 bind the NRSE with lower affinity or have reduced repressor activity.
NCBI Gene states that REST can act as an oncogene or a tumour suppressor depending on cellular context. Its splicing is also needed for hearing in inner-ear hair cells. Mouse and rat both have a Rest ortholog, so rodent models can be used to study it.
Other zinc finger transcription factors, neurogenesis regulators and splicing factors with products at Assay Genie.
Gene and protein annotations from HGNC, NCBI Gene and UniProt Q13127; product specifications from Assay Genie datasheets.