Chromatin changes trigger laminin genes dysregulation in aging kidneys

Aging
Oleg DenisenkoKarol Bomsztyk

Abstract

Dysregulation of gene expression is a hallmark of aging. We examined epigenetic mechanisms that mediate aberrant expression of laminin genes in aging rat kidneys. In old animals, no alterations were found in the levels of abundant laminin mRNAs, whereas Lama3, b3, and c2 transcripts were increased compared to young animals. Lamc2 showed the strongest changes at the mRNA and protein levels. Lamc2 upregulation was transcriptional, as indicated by the elevated RNA polymerase II density at the gene. Furthermore, aging is associated with the loss of H3K27m3 and 5mC silencing modifications at the Lamc2 gene. Western blot analysis revealed no changes in cellular levels of H3K27m3 and cognate enzyme Ezh2 in old kidneys. Thus, the decrease in H3K27m3 at Lamc2 resulted from the re-distribution of this mark among genomic sites. Studies in kidney cells in vitro showed that reducing H3K27m3 density with Ezh2 inhibitor had no effect on Lamc2 expression, suggesting that this modification plays little role in gene upregulation in aging kidney. In contrast, treatment with DNA methylation inhibitor 2'-deoxy-5-azacytidine was sufficient to upregulate Lamc2 gene. We suggest that the loss of 5mC at silenced laminin genes drives their de-repression ...Continue Reading

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Citations

Jul 4, 2019·Cells·Raquel Romero-BuenoAgnieszka Dobrzynska
May 28, 2020·Frontiers in Immunology·Rossana FranzinGiuseppe Castellano
Jan 30, 2021·Nucleic Acids Research·Sam KintOleg Denisenko
Mar 9, 2021·Frontiers in Physiology·Tingting LiShougang Zhuang
Jun 27, 2021·Biochimica Et Biophysica Acta. Gene Regulatory Mechanisms·Agnes MendoncaChongli Yuan

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Methods Mentioned

BETA
ChIP
PCR
immunoprecipitation

Software Mentioned

SDS Enterprise Database

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