REST: A mammalian silencer protein that restricts sodium channel gene expression to neurons

Chong, Jayhong A.; Tapia-Ramı́rez, José; Kim, Sandra; Toledo‐Aral, Juan José; Yi, Zheng; Boutros, Michael; Altshuller, Yelena M.; Frohman, Michael A.; Kraner, Susan D.; Mandel, Gail

doi:10.1016/0092-8674(95)90298-8

Cited by 1,010 publications

(971 citation statements)

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“…This GLIKruppel zinc finger transcription factor was first described as a silencer of neuronal genes outside the central nervous system, since its expression is restricted to non-neuronal cells and undifferentiated neural progenitors, allowing genes encoding fundamental neuronal traits to be exclusively expressed in mature neurons [2,3]. Target genes possess a 21 bp cis element called RE-1 or neuron restrictive silencer element, to which REST binds to inhibit expression.…”

Section: Introductionmentioning

confidence: 99%

Functional significance of repressor element 1 silencing transcription factor (REST) target genes in pancreatic beta cells

et al. 2008

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Aims/hypothesis The expression of several neuronal genes in pancreatic beta cells is due to the absence of the transcription factor repressor element 1 (RE-1) silencing transcription factor (REST). The identification of these traits and their functional significance in beta cells has only been partly elucidated. Herein, we investigated the biological consequences of a repression of REST target genes by expressing REST in beta cells. Methods The effect of REST expression on glucose homeostasis, insulin content and release, and beta cell mass was analysed in transgenic mice selectively expressing REST in beta cells. Relevant target genes were identified in INS-1E and primary beta cells expressing REST. Results Transgenic mice featuring a beta cell-targeted expression of REST exhibited glucose intolerance and reduced beta cell mass. In primary beta cells, REST repressed several proteins of the exocytotic machinery, including synaptosomal-associated protein (SNAP) 25, synaptotagmin (SYT) IV, SYT VII, SYT IX and complexin II; it impaired first and second phases of insulin secretion. Using RNA interference in INS-1E cells, we showed that SYT IV and SYT VII were implicated in the control of insulin release.

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Section: Introductionmentioning

confidence: 99%

Functional significance of repressor element 1 silencing transcription factor (REST) target genes in pancreatic beta cells

et al. 2008

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“…REST is located on chromosome 4q12, consists of 4 exons, and encodes a 1,097-amino acid protein 15,16 (Figures 2B and 2C). REST is a zinc finger protein that regulates gene expression throughout the body.…”

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confidence: 99%

“…REST is a zinc finger protein that regulates gene expression throughout the body. 16,17 It has a critical function as a transcriptional repressor during embryonic development and neurogenesis so it is also called neuron-restrictive silencer element. 15 Additionally, REST has different roles in several cellular mechanisms, such as oncogenic and tumor-suppressor functions, hematopoietic, cardiac and osteoblast differentiation, and effects on chromatin-modifying enzymes.…”

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confidence: 99%

REST Final-Exon-Truncating Mutations Cause Hereditary Gingival Fibromatosis

Bayram

White

Elçioğlu

et al. 2017

The American Journal of Human Genetics

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Hereditary gingival fibromatosis (HGF) is the most common genetic form of gingival fibromatosis that develops as a slowly progressive, benign, localized or generalized enlargement of keratinized gingiva. HGF is a genetically heterogeneous disorder and can be transmitted either as an autosomal-dominant or autosomal-recessive trait or appear sporadically. To date, four loci (2p22.1, 2p23.3-p22.3, 5q13-q22, and 11p15) have been mapped to autosomes and one gene (SOS1) has been associated with the HGF trait observed to segregate in a dominant inheritance pattern. Here we report 11 individuals with HGF from three unrelated families. Whole-exome sequencing (WES) revealed three different truncating mutations including two frameshifts and one nonsense variant in RE1-silencing transcription factor (REST) in the probands from all families and further genetic and genomic analyses confirmed the WES-identified findings. REST is a transcriptional repressor that is expressed throughout the body; it has different roles in different cellular contexts, such as oncogenic and tumor-suppressor functions and hematopoietic and cardiac differentiation. Here we show the consequences of germline final-exontruncating mutations in REST for organismal development and the association with the HGF phenotype.

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“…The present results also provide insight into the regulation of β-tubulin III by the zinc-finger transcription factor NRSF (neuron-restrictive silencing factor), whose function, in part, is to repress the expression of neuron-specific genes in non-neuronal cells (Chong et al , 1995;Lunyak and Rosenfeld, 2005;Schoenherr and Anderson, 1995). NRSF binds to a conserved 21 bp element called an NRSE (neuron-restrictive silencer element), and exerts its influence by recruiting enzymes that alter chromatin structure (Lunyak and Rosenfeld, 2005).…”

Section: Discussionmentioning

confidence: 68%

A transgenic mouse Class‐III β tubulin reporter using yellow fluorescent protein

Liu

Geisert

Frankfurter

et al. 2007

Genesis

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A yellow fluorescence protein (YFP) reporter construct was cloned downstream of the β-tubulin III promoter and injected to produce two founder lines of transgenic mice. YFP expression was observed in many regions of the developing peripheral and central nervous system. YFP expression was first observed in the peripheral and central nervous system as early as embryonic day 9.0. There was a dramatic increase in the number of neuronal systems expressing YFP through P0. Then as the animals reached adult age the expression levels decreased, but many neurons still show YFP expression, noteably in regions of the brain undergoing adult neurogenesis, i.e., the rostral migratory stream and sub-granular layer of the dentate gyrus. This reporter-based staining was compared with anti-class-III β-tubulin immunocytochemistry and shown to closely parallel the expression of the endogenous protein. These transgenic lines should provide unique models to study in vivo and in vitro neurodevelopment.

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REST: A mammalian silencer protein that restricts sodium channel gene expression to neurons

Cited by 1,010 publications

References 33 publications

Functional significance of repressor element 1 silencing transcription factor (REST) target genes in pancreatic beta cells

Functional significance of repressor element 1 silencing transcription factor (REST) target genes in pancreatic beta cells

REST Final-Exon-Truncating Mutations Cause Hereditary Gingival Fibromatosis

A transgenic mouse Class‐III β tubulin reporter using yellow fluorescent protein

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