Alterations in chromatin are associated with increases in collagen III expression in aging nephropathy

Abrass CK, Hansen K, Popov V, Denisenko O. Alterations in chromatin are associated with increases in collagen III expression in aging nephropathy. Am J Physiol Renal Physiol 300: F531-F539, 2011. First published July 7, 2010; doi:10.1152/ajprenal.00237.2010.-Aging nephropathy is a slowly progressive fibrotic process that affects all compartments of the kidney and eventually impairs kidney function; however, little is known about the mechanisms that contribute to this process. These studies examined the epigenetic control of expression of collagen III (Col3a1), a matrix protein that contributes to kidney fibrosis. Using real-time PCR, Western blotting, and chromatin immunoprecipitation assay of kidneys harvested from 4- and 24-mo-old ad libitum-fed F344 rats, we found increased transcription of Col3a1 that was associated with increased RNA polymerase II recruitment despite elevated posttranslational histone modification (H3K27me3) normally associated with gene silencing. A reduction in the density of another repressive modification (H3K9me3) at the Col3a1 locus in aged rats suggests that cooperation between Polycomb-and heterochromatin-mediated systems are required to maintain repression of the Col3a1 gene. These findings demonstrate alterations in epigenetic control of gene expression in association with the fibrosis of aging nephropathy.