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Incorporating histone H2B variants into chromatin modifies chromatin accessibility to induce the epithelial-to-mesenchymal transition in breast cancer [CUT&RUN]

ABSTRACT: Histones scaffold genomic DNA and regulate access to the transcriptional machinery. However, naturally occurring histone variants can alter histone-DNA interactions, DNA and histone modifications, and the chromatin interactome. Hence, alterations in histone variant deposition can disrupt chromatin, and are increasingly recognized as a way to trigger various disease (including cancer). While significant attention has been placed on the biochemical and functional roles of H2A and H3 variants, H2B variants remain largely understudied. Here, we show that H2B variants are dysregulated in breast cancer and that certain variants are associated with specific breast cancer subtypes. HIST1H2BO overexpression (in particular) is more common in Asian, African American/Black, and young female populations and is associated with a worse prognosis. In vitro, H2B1O compacts chromatin, and incorporating H2B1O into chromatin activates pro-inflammatory and oncogenic pathways and the epithelial-to-mesenchymal transition (EMT), and generates resistance to first-line chemotherapeutic agents. Thus, H2B1O acts much like an onco-histone, with H2B variant expression being a prognostic biomarker for breast cancer and a potential new target for drug therapies to enhance treatment efficacy.

ORGANISM(S): Homo sapiens

PROVIDER: GSE285390 | GEO | 2026/02/11

REPOSITORIES: GEO

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Incorporating histone H2B variants into chromatin modifies chromatin accessibility to induce the epithelial-to-mesenchymal transition in breast cancer [RNA]

Project description:Histones scaffold genomic DNA and regulate access to the transcriptional machinery. However, naturally occurring histone variants can alter histone-DNA interactions, DNA and histone modifications, and the chromatin interactome. Hence, alterations in histone variant deposition can disrupt chromatin, and are increasingly recognized as a way to trigger various disease (including cancer). While significant attention has been placed on the biochemical and functional roles of H2A and H3 variants, H2B variants remain largely understudied. Here, we show that H2B variants are dysregulated in breast cancer and that certain variants are associated with specific breast cancer subtypes. HIST1H2BO overexpression (in particular) is more common in Asian, African American/Black, and young female populations and is associated with a worse prognosis. In vitro, H2B1O compacts chromatin, and incorporating H2B1O into chromatin activates pro-inflammatory and oncogenic pathways and the epithelial-to-mesenchymal transition (EMT), and generates resistance to first-line chemotherapeutic agents. Thus, H2B1O acts much like an onco-histone, with H2B variant expression being a prognostic biomarker for breast cancer and a potential new target for drug therapies to enhance treatment efficacy.

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