A Study Of H3K9me3 And H3K27me3 In Cell Senescence

Cell senescence refers to a relatively stable state in which cells enter the cell cycle without irreversible loss of proliferative capacity,and is the inevitable fate of normal cells.The process of cellular aging is accompanied by a variety of changes including cell cycle arrest,chromatin structural changes,secretory phenotypic changes,and reduced permeability and intracellular material settling.Cellular senescence induced by various factors such as oncogene RAS is accompanied by the production of(senescence-associated heterochromatic foci,SAHF)which is an important morphological feature of cell senescence.Among them,histones H3K9me3 and H3K27me3 are distributed in a ring-like arrangement..So what is the role of the heterochromatin markers H3K9me3 and H3K27me3 in the SAHF structure? What is the role of H3K9me3 and H3K27me3 in SAHF formation and cell senescence?In our experiments,it was found that under the RAS-induced cell senescence system,the overexpression of histone demethylase JMJD2D and the interference of the Polycomb complex component SUZ12 together inhibited the heterochromatin markers H3K9me3 and H3K27me3,and the cells remained A SAHF-like structure will be formed.After that,we did use JMJD2D and sh SUZ12 in IMR90 cells not in the RAS system to inhibit H3K9me3 and H3K27me3,and the cells showed obvious aging.Surprisingly,SAHF-like structures will still form.Further studies have found that the formation of this SAHF-like structure is dependent on HMGAs.On the other hand,we also focused on the combined inhibition of H3K9me3 and H3K27me3 on senescence-associated secretory phenotype.Some types of senescence-associated secretory phenotype(SASP)secreted by senescent cells are complex components such as growth factors,chemokines,inflammatory factors,and matrix remodeling enzymes.On the one hand,SASP can protect the body such as boosting immunity and inhibiting cancer development.However,on the other hand,it can promote the occurrence and development of tumors.It is a double-edged sword.We found that unlike RAS-induced cell senescence,double inhibition of H3K9me3 and H3K27me3 induced cell senescence was not accompanied by up-regulation of the classical components of SASP,IL6 and IL8.In conclusion,combined inhibition of H3K9me3 and H3K27me3 does not upregulate SASP while inducing cell senescence,which may be a favorable event for cancer treatment and provide a new treatment strategy for clinical treatment of cancer.