Alterations in chromatin are associated with increases in collagen III expression in aging nephropathy.
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.
Abrass
Christine K
CK
Primary and Specialty Care Medicine, Department of Veterans Affairs Puget Sound Health Care System, Seattle, Washington, USA. cabrass@u.washington.edu
Hansen
Kim
K
Popov
Viorica
V
Denisenko
Oleg
O
D000375:Aging / Q000235:genetics / Q000473:pathology*; D000818:Animals; D002843:Chromatin / Q000378:metabolism* / Q000648:ultrastructure; D024061:Collagen Type III / Q000235:genetics*; D057890:Epigenomics; D015870:Gene Expression; D020868:Gene Silencing; D056426:Genetic Loci; D006657:Histones / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D007674:Kidney Diseases / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D011499:Protein Processing, Post-Translational; D012319:RNA Polymerase II / Q000032:analysis / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344
D002843:Chromatin; D024061:Collagen Type III; D006657:Histones; D012319:RNA Polymerase II