机械力学调控多梳基因介导的基因沉默..pptx

Mechanical regulation of transcription controlspolycomb-mediated gene silencing duringlineage commitment;Very little is known about the molecular principles underlying the mechanical control of lineage specification and maintenance. Non-muscle myosins(NM):a family of motor proteins that generate forces by moving antiparallel actin filaments, are central players in force generation and sensing. Polycomb repressive complex 2 (PRC2)： catalyses dimethylation H3K27me3 through the methyltransferase activity of Ezh1/Ezh26,7, recognizes the untranscribed state of genes to subsequently maintain their repression. ;Mechanical strain induces transcriptional repression;5-Ethynyl uridine (EU) incorporation assays show reduced levels of nascent RNA after 12 h of strain;Increased H3K27me3 and decreased RNAPII-S2p in cells subjected to strain for 12 h;;Mechanical strain regulates H3K27me3 through localized actinremodelling controlled by Emd and NMIIA;Strain increased signal of Emd at the outer nuclear membrane (ONM) of strained cells whereas the relative signal at the inner nuclear membrane (INM) is decreased ,accumulation of F-actin around the nucleus . RNAi-mediated depletion of Emd (Emd siRNA) prevents actin polymerization at this site.;;Strain induces Emd-mediated rearrangements of chromatin accompanied by a switch from H3K9me2,3 to H3K27me3.;Increase nuclear actin levels promote productive RNAPII elongationand offset H3K27me3-mediated silencing.;Strain-induced remodelling of constitutive heterochromatin is independent of the actin-mediated regulation of RNAPII.;Force-mediated adjustment of transcription regulates SC lineage commitment;NMIIA activity regulates kinetics of differentiation in vivo;G-actin levels in basal keratinocytes of Myh9EKO epidermis increased, no differences in the protein levels of the two proteins in strained cells.;Discussion;Thank you