HBO1 functions as an epigenetic barrier to hepatocyte plasticity and reprogramming during liver injury.
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Abstract | Hepatocytes can reprogram into biliary epithelial cells (BECs) during liver injury, but the underlying epigenetic mechanisms remain poorly understood. Here, we define the chromatin dynamics of this process using single-cell ATAC-seq and identify YAP/TEAD activation as a key driver of chromatin remodeling. An in vivo CRISPR screen highlights the histone acetyltransferase HBO1 as a critical barrier to reprogramming. HBO1 is recruited by YAP to target loci, where it promotes histone H3 lysine 14 acetylation (H3K14ac) and engages the chromatin reader zinc-finger MYND-type containing 8 (ZMYND8) to suppress YAP/TEAD-driven transcription. Loss of HBO1 accelerates chromatin remodeling, enhances YAP binding, and enables a more complete hepatocyte-to-BEC transition. Our findings position HBO1 as an epigenetic brake that restrains YAP-mediated reprogramming, suggesting that targeting HBO1 may enhance hepatocyte plasticity for liver regeneration. |
Year of Publication | 2025
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Journal | Cell stem cell
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Volume | 32
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Issue | 6
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Pages | 990-1005.e8
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Date Published | 06/2025
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ISSN | 1875-9777
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DOI | 10.1016/j.stem.2025.04.010
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PubMed ID | 40403721
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