title: Alterations in chromatin are associated with increases in collagen III expression in aging nephropathy.
abstract: 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.
authors.affiliation: Primary and Specialty Care Medicine, Department of Veterans Affairs Puget Sound Health Care System, Seattle, Washington, USA. cabrass@u.washington.edu
authors.forename: Christine K
authors.initials: CK
authors.lastname: Abrass
authors.forename: Kim
authors.initials: K
authors.lastname: Hansen
authors.forename: Viorica
authors.initials: V
authors.lastname: Popov
authors.forename: Oleg
authors.initials: O
authors.lastname: Denisenko
mesh_terms: 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
chemical_list: D002843:Chromatin; D024061:Collagen Type III; D006657:Histones; D012319:RNA Polymerase II