Mechanism of REST/NRSF regulation of clustered protocadherin α genes | Zendy

Yuanxiao Tang | Zendy; Zhilian Jia | Zendy; Honglin Xu | Zendy; LinTai Da | Zendy; Qiang Wu | Zendy

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Mechanism of REST/NRSF regulation of clustered protocadherin α genes

Author(s) -

Yuanxiao Tang,

Zhilian Jia,

Honglin Xu,

LinTai Da,

Qiang Wu

Publication year - 2021

Publication title -

nucleic acids research

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 9.008

H-Index - 537

eISSN - 1362-4954

pISSN - 0305-1048

DOI - 10.1093/nar/gkab248

Subject(s) - protocadherin , biology , enhancer , repressor , gene , genetics , transcription factor , gene silencing , regulation of gene expression , transcriptional regulation , transcription (linguistics) , silencer , cadherin , cell , mechanical engineering , linguistics , philosophy , engineering , inlet

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 PCDHα genes. Thus, REST/NRSF represses PCDHα gene expression through directional binding to a repertoire of NRSEs within the distal enhancer and variable target genes.

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