HBO1 functions as an epigenetic barrier to hepatocyte plasticity and reprogramming during liver injury. Cell Stem Cell. 2025 May 19.

Citation

Yuan WC, Earl AS, Ma S, Alcedo K, Russell JO, Duarte FM, Chu YT, Chang PC, Chen HY, Chi HH, Zhu Q, Rodriguez-Fraticelli AE, Patel SH, Lee YR, Buenrostro JD, Camargo FD. 2025. HBO1 functions as an epigenetic barrier to hepatocyte plasticity and reprogramming during liver injury. Cell stem cell. 32(6):990-1005.e8. Pubmed: 40403721 DOI:S1934-5909(25)00177-8

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.

Related Faculty

Jason Buenrostro, Ph.D.

Buenrostro Lab

The Buenrostro lab is broadly dedicated to advancing our knowledge of gene regulation and the downstream consequences on cell fate decisions.