Multi-omics profiling of cholangiocytes reveals chromatin state dynamics during hepatic cystogenesis in polycystic liver disease (ChIP-Seq)

Through genome-wide profiling of chromatin dynamics, we revealed a profound increase of global chromatin accessibility and a switch from H3K9me3 to H3K9ac on cis-regulatory DNA elements of cyst-associated genes during cystogenesis. In an integrated epigenomic and transcriptomic analysis, we identified a transcription factor network associated with dynamic shifts in chromatin states. Functionally, we showed that inhibition of H3K9ac acetyltransferase or H3K9me3 demethylase restored chromatin states and gene expression program to slow cyst growth in PLD mice. Overall design: Chromatin immunoprecipitation coupled with deep sequencing (ChIP-seq) in primary WT and PLD cholangiocytes.