Format

Send to

Choose Destination
Genes Dev. 2015 Jul 1;29(13):1362-76. doi: 10.1101/gad.263707.115.

H3K36 methylation promotes longevity by enhancing transcriptional fidelity.

Author information

1
Department of Cell and Developmental Biology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA;
2
Department of Cell and Developmental Biology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA; Huffington Center on Aging, Baylor College of Medicine, Houston, Texas 77030, USA;
3
High-Throughput Biology Center, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA;
4
Huffington Center on Aging, Baylor College of Medicine, Houston, Texas 77030, USA;
5
Department of Biology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA;
6
Department of Pathology, University of Washington, Seattle, Washington 98195, USA;
7
The Buck Institute of Research on Aging, Novato, California 94945, USA;
8
High-Throughput Biology Center, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA; Institute for Systems Genetics, New York University Langone Medical Center, New York, New York 10016, USA.

Abstract

Epigenetic mechanisms, including histone post-translational modifications, control longevity in diverse organisms. Relatedly, loss of proper transcriptional regulation on a global scale is an emerging phenomenon of shortened life span, but the specific mechanisms linking these observations remain to be uncovered. Here, we describe a life span screen in Saccharomyces cerevisiae that is designed to identify amino acid residues of histones that regulate yeast replicative aging. Our results reveal that lack of sustained histone H3K36 methylation is commensurate with increased cryptic transcription in a subset of genes in old cells and with shorter life span. In contrast, deletion of the K36me2/3 demethylase Rph1 increases H3K36me3 within these genes, suppresses cryptic transcript initiation, and extends life span. We show that this aging phenomenon is conserved, as cryptic transcription also increases in old worms. We propose that epigenetic misregulation in aging cells leads to loss of transcriptional precision that is detrimental to life span, and, importantly, this acceleration in aging can be reversed by restoring transcriptional fidelity.

KEYWORDS:

H3K36 methylation; aging; cryptic transcription; epigenetics

PMID:
26159996
PMCID:
PMC4511212
DOI:
10.1101/gad.263707.115
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center