RRC ID 46416
Author Ni Z, Ebata A, Alipanahiramandi E, Lee SS.
Title Two SET domain containing genes link epigenetic changes and aging in Caenorhabditis elegans.
Journal Aging Cell
Abstract Changes in epigenetic status and chromatin structure have been shown to associate with aging in many organisms. Here, we report an RNAi screen of putative histone methyltransferases and demethylases in wild-type Caenorhabditis elegans using reproduction inhibitor. We identified six genes that when inactivated by RNAi, consistently extend lifespan. Five of these genes do not require germline proliferation to affect lifespan. We further characterized two of these genes, the highly homologous SET domain containing genes, set-9 and set-26. They share redundant functions in maintaining normal lifespan, while exhibiting differential tissue expression patterns. Furthermore, we found that set-9 and set-26 partially act through the Forkhead box O (FOXO) transcription factor, DAF-16, to modulate lifespan. Interestingly, inactivation of somatic SET-26 alone results in a robust lifespan extension and alters the levels of histone H3 protein and the repressive histone marks, H3K9me3 and H3K27me3, in an age-dependent manner. We hypothesize that inactivation of SET-26 triggers compensation mechanisms to restore repressive chromatin structure and hence affects chromatin stability to promote longevity.
Volume 11(2)
Pages 315-25
Published 2012-4-1
DOI 10.1111/j.1474-9726.2011.00785.x
PMID 22212395
PMC PMC3306474
MeSH Aging* Animals Caenorhabditis elegans / genetics* Caenorhabditis elegans / physiology Epigenesis, Genetic* Mutation Organ Specificity RNA Interference
IF 7.238
Times Cited 51
C.elegans tm2467 tm3505 tm3674