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bioRxiv · 10.1101/2021.03.06.434230

Mechanism of REST/NRSF Regulation of Clustered Protocadherin Alpha Genes

Tang, Y.·Jia, Z.·Xu, H.·Da, L.-T.·Wu, Q.
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Abstract

Repressor 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 the HS5-1 enhancer leads to the decrease of long-range enhancer-promoter interactions and downregulation of the clustered PCDH genes. Thus, REST/NRSF represses PCDH gene expression through directional binding to a repertoire of NRSEs within the distal enhancer and variable target genes.

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Tang, Y., Jia, Z., Xu, H., Da, L.-T., Wu, Q.. 2021-03-07. Mechanism of REST/NRSF Regulation of Clustered Protocadherin Alpha Genes. https://doi.org/10.1101/2021.03.06.434230

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