Abstract
Beta cells are defined by the genes they express, many of which are specific to this cell type, and ensure a specific set of functions. Beta cells are also defined by a set of genes they should not express (in order to function properly), and these genes have been called forbidden genes. Among these, the transcriptional repressor RE-1 Silencing Transcription factor (REST) is expressed in most cells of the body, excluding most populations of neurons, as well as pancreatic beta and alpha cells. In the cell types where it is expressed, REST represses the expression of hundreds of genes that are crucial for both neuronal and pancreatic endocrine function, through the recruitment of multiple transcriptional and epigenetic co-regulators. REST targets include genes encoding transcription factors, proteins involved in exocytosis, synaptic transmission or ion channeling, and non-coding RNAs. REST is expressed in the progenitors of both neurons and beta cells during development, but it is down-regulated as the cells differentiate. Although REST mutations and deregulation have yet to be connected to diabetes in humans, REST activation during both development and in adult beta cells leads to diabetes in mice.
Highlights
repressor element-1 (RE-1) Silencing Transcription factor (REST) is a transcription factor that represses numerous genes that are essential to the function of beta cells
This repressor was called RE-1 Silencing Transcription factor (REST) because it binds to a DNA element called repressor element-1 (RE-1) located in the rat Scn2a2 gene (Chong et al, 1995; Figure 1)
The cell-specificity of REST target occupancy has been resolved at the genome-wide level using chromatin immunoprecipitation (ChIP)-seq or ChIP-chip experiments, by comparing REST regulatory networks between embryonic stem cells (ESC) and neural stem cells (NSC; Johnson et al, 2008), or between different neuronal and non-neuronal cell lines (Bruce et al, 2009) and is further discussed below
Summary
Beta cells are defined by the genes they express, many of which are specific to this cell type, and ensure a specific set of functions. Beta cells are defined by a set of genes they should not express (in order to function properly), and these genes have been called forbidden genes. The transcriptional repressor RE-1 Silencing Transcription factor (REST) is expressed in most cells of the body, excluding most populations of neurons, as well as pancreatic beta and alpha cells. REST targets include genes encoding transcription factors, proteins involved in exocytosis, synaptic transmission or ion channeling, and non-coding RNAs. REST is expressed in the progenitors of both neurons and beta cells during development, but it is down-regulated as the cells differentiate.
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