Epigenetic changes play critical role in age-associated dysfunctions of the liver.

ABSTRACT: CCAAT/Enhancer Binding Proteins family proteins are important regulators of liver functions. Here, we show the critical role of C/EBPα-mediated chromatin remodeling in the age-associated dysfunctions of the liver and in the maintenance of physiological homeostasis. Because ph-S193 isoform of C/EBPα is increased in livers of old mice, we have generated C/EBPα-S193D knockin mice, which mimic the ph-S193 isoform of C/EBPα. Analyses of these mice showed that the S193D mutation causes chromatin remodeling leading to histological appearance of 'foci-like' nodules, which are also observed in livers of old mice. These 'foci-like' structures contain K9 trimethylated histone H3, a marker of heterochromatin. The increase of heterochromatin regions in S193D mice correlates with the elevation of S193D-

SUBMITTER: Jin J 

PROVIDER: S-EPMC3046424 | biostudies-literature | 2010 Oct

REPOSITORIES: biostudies-literature