Screen and functional analysis of epigenetic factors that regulate cellular senescence
Description: Senescent cells exhibit higher mitochondrial activities compared with proliferating cells, which contributes to the production and secretion of senescence-associated secretory proteins. The researchers performed gene-knockdown screen and revealed that depletion of SETD8 or NSD2 histone methyltransferase cause senescence and senescence-associated abnormal activation of mitochondrial respiration. Mechanistically, depletion of SETD8 decreased the levels of histone H4 lysine 20 mono-methylation at p16 and p21 gene loci and activated their expression. Then, p16 and p21 activated retinoblastoma protein (RB) to enhance mitochondrial respiration. Loss of NSD2 also activated p21 and RB to induce senescence. In summary, our data revealed that multiple epigenetic regulators contribute to preventing senescence and senescence-associated metabolic remodeling by maintaining p16/p21-RB pathway.
Amount: ¥2,730,000
Funding type: fellowship
Funder scheme: Grant-in-Aid for Research Activity Start-up
Start date: 2017-08-25
End date: 2019-03-31
Investigator: Hiroshi Tanaka
Institution: Kumamoto University
Funded outputs count: 1
Funder award ID: 17H06969
OpenAlex ID: G1877077160