Hdac3 is essential for the maintenance of chromatin structure and genome stability

Deletion of Hdac3 impaired DNA repair and greatly reduced chromatin compaction and heterochromatin content. Liver-specific deletion of Hdac3 culminated in hepatocellular carcinoma. The loss of genomic stability and the impaired response to DNA damage suggested that a high mutation rate stimulated the development of HCC. To begin to assess what pathways were involved in the formation of HCC, we performed gene expression analysis using cDNA microarrys. In the array data, we noted the enhanced expression of c-Myc, a commonly over expressed oncogene and signatures consistent with activation of the Ras pathway and impairment of the p53 pathway were also identified in this analysis. We isolated total RNA from livers obtained from ~10 month old control (Hdac3FL/+; AlbCre+) or null (Hdac3FL/-; AlbCre+) male mice.