Super-silencers are crucial for development and carcinogenesis in B cells.

ABSTRACT: The strength of the repressive histone H3K27me3 signal varies across silencers. Focusing on regions with unusually strong signals-super-silencers-we show that B-cell super-silencers are initially linked to gene upregulation in development, with target genes highly expressed in stem cells. About 13% of B-cell super-silencers convert to super-enhancers in B-cell lymphoma; 22% of these recur in over half of patients. Genes like BCL6 and BACH2 tied to these conversions are downregulated faster by JQ1, a super-enhancer-disrupting anti-cancer agent. Super-silencers are enriched for B-cell cancer-associated variants-both somatic and germline-and translocation breakpoints, exceeding levels in other regulatory elements like CTCF  binding sites. Over 80% of B-cell lymphoma t(3;14)(q27;q32) transloca

SUBMITTER: Huang D 

PROVIDER: S-EPMC12462470 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature