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Mechanism of REST/NRSF Regulation of Clustered Protocadherin α Genes
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ABSTRACTRepressor element-1 silencing transcription factor (REST) or neuron-restrictive silencer factor (NRSF) is a zinc-finger (ZF) containing transcriptional repressor that recognizes thousands of neuron-restrictive silencer elements (NRSEs) in mammalian genomes. How REST/NRSF regulates gene expression remains incompletely understood. Here, we investigate the binding pattern and regulation mechanism of REST/NRSF in the clustered protocadherin (PCDH) genes. We find that REST/NRSF directionally forms base-specific interactions with NRSEs via tandem ZFs in an anti-parallel manner but with striking conformational changes. In addition, REST/NRSF recruitment to theHS5-1enhancer leads to the decrease of long-range enhancer-promoter interactions and downregulation of the clusteredPCDHαgenes. Thus, REST/NRSF repressesPCDHαgene expression through directional binding to a repertoire of NRSEs within the distal enhancer and variable target genes.
Title: Mechanism of REST/NRSF Regulation of Clustered Protocadherin α Genes
Description:
ABSTRACTRepressor element-1 silencing transcription factor (REST) or neuron-restrictive silencer factor (NRSF) is a zinc-finger (ZF) containing transcriptional repressor that recognizes thousands of neuron-restrictive silencer elements (NRSEs) in mammalian genomes.
How REST/NRSF regulates gene expression remains incompletely understood.
Here, we investigate the binding pattern and regulation mechanism of REST/NRSF in the clustered protocadherin (PCDH) genes.
We find that REST/NRSF directionally forms base-specific interactions with NRSEs via tandem ZFs in an anti-parallel manner but with striking conformational changes.
In addition, REST/NRSF recruitment to theHS5-1enhancer leads to the decrease of long-range enhancer-promoter interactions and downregulation of the clusteredPCDHαgenes.
Thus, REST/NRSF repressesPCDHαgene expression through directional binding to a repertoire of NRSEs within the distal enhancer and variable target genes.
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