Short tandem repeats are important contributors to silencer elements in T cells.
Fiche publication
Date publication
mars 2023
Journal
Nucleic acids research
Auteurs
Membres identifiés du Cancéropôle Est :
Dr SEXTON Thomas
Tous les auteurs :
Hussain S, Sadouni N, van Essen D, Dao LTM, Ferré Q, Charbonnier G, Torres M, Gallardo F, Lecellier CH, Sexton T, Saccani S, Spicuglia S
Lien Pubmed
Résumé
The action of cis-regulatory elements with either activation or repression functions underpins the precise regulation of gene expression during normal development and cell differentiation. Gene activation by the combined activities of promoters and distal enhancers has been extensively studied in normal and pathological contexts. In sharp contrast, gene repression by cis-acting silencers, defined as genetic elements that negatively regulate gene transcription in a position-independent fashion, is less well understood. Here, we repurpose the STARR-seq approach as a novel high-throughput reporter strategy to quantitatively assess silencer activity in mammals. We assessed silencer activity from DNase hypersensitive I sites in a mouse T cell line. Identified silencers were associated with either repressive or active chromatin marks and enriched for binding motifs of known transcriptional repressors. CRISPR-mediated genomic deletions validated the repressive function of distinct silencers involved in the repression of non-T cell genes and genes regulated during T cell differentiation. Finally, we unravel an association of silencer activity with short tandem repeats, highlighting the role of repetitive elements in silencer activity. Our results provide a general strategy for genome-wide identification and characterization of silencer elements.
Référence
Nucleic Acids Res. 2023 03 17;: