SRP310451 PRJNA714118 GSE168833 Wilson disease: intersecting DNA methylation and histone acetylation mechanisms affect gene expression regulation in a mouse model of hepatic copper accumulation [RNA-Seq] Prior investigations of DNA methylation differences in WD liver and blood and in a WD mouse model revealed an epigenetic signature of WD that included the histone deacetylase, HDAC5. To test the hypothesis that histone deacetylation and acetylation might be altered with respect to copper overload and aberrant DNA methylation in WD, we used the Jackson Laboratory toxic milk model (tx-j) of WD to study the involvement of Class IIa histone deacetylases (HDAC4 and HDAC5) and histone acetylation (H3K9ac and H3K27ac), and the effects of copper chelator D-penicillamine (PCA) and/or methyl group donor choline on histone modification. Next, we related acetylation profiles of H3K27ac to gene expression changes in wilson disease by ChIP and RNA-seq. Overall design: Our study represents the liver transcriptomes of tx-j: mice model of WD by RNA-seq technology Coordinately upregulated and downregulated genes with H3K27 acetylation were identified to study the transcription factors and biological pathways involved in WD. We demonstrate a role for histone deacetylases at the interface between nutrition, histone acetylation, DNA methylation, and gene expression regulation affecting liver disease severity in WD GSE168833 pubmed 34098115 parent_bioproject PRJNA714683