Whole-genome functional characterization of RE1 silencers using a modified massively parallel reporter assay.

ABSTRACT: Both upregulation and downregulation by cis-regulatory elements help modulate precise gene expression. However, our understanding of repressive elements is far more limited than activating elements. To address this gap, we characterized RE1, a group of transcriptional silencers bound by REST, at genome-wide scale using a modified massively parallel reporter assay (MPRAduo). MPRAduo empirically defined a minimal binding strength of REST (REST motif-intrinsic value [m-value]), above which cofactors colocalize and silence transcription. We identified 1,500 human variants that alter RE1 silencing and found that their effect sizes are predictable when they overlap with REST-binding sites above the m-value. Additionally, we demonstrate that non-canonical REST-binding motifs exhibit silenc

SUBMITTER: Mouri K 

PROVIDER: S-EPMC9903721 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature