in the nucleus which inhibits protein phosphatase-1, thereby promoting phosphorylation. Blocking this phosphorylation event at serine 10 on H3 was able to diminish the behavioral responses to both cocaine and morphine and blocked conditioned place preference for cocaine (Stipanovich et al., 2008). In the periphery, ethanol and its breakdown product, acetaldehyde, activate various MAP kinase-signaling pathways (Aroor & Shukla, 2004). In primary rat hepatocytes, ethanol and acetaldehyde were shown to increase phosphorylation of histone H3 at serine 10 and serine 28 mediated by p38 MAPK in the nucleus (Lee & Shukla, 2007). In the same model it was also shown that ethanol upregulates the activating marks H3K9 acetylation and H3K4 dimethylation and down-regulates H3K9 dimethylation (Pal-Bhadra et al., 2007; Park et al., 2003). This illustrates the complex modulation of histone H3 at different residues by ethanol in the liver, which may give rise to the various pathologic states resulting due to chronic ethanol ingestion contributing to alcoholic liver disease.
