Our results provide a general strategy for genome-wide identification and characterization of silencer elements.

Finally, we unravel an association of silencer activity with short tandem repeats, highlighting the role of repetitive elements in silencer activity. 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.

Identified silencers were associated with either repressive or active chromatin marks and enriched for binding motifs of known transcriptional repressors. We assessed silencer activity from DNase hypersensitive I sites in a mouse T cell line. Here, we repurpose the STARR-seq approach as a novel high-throughput reporter strategy to quantitatively assess silencer activity in mammals. 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. Gene activation by the combined activities of promoters and distal enhancers has been extensively studied in normal and pathological contexts.

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.

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