| Gene name: | TGFB1 |
| Aging type: | Accelerate |
| Aging characteristic: |
| Tissue type: | -- |
| Cell name: | MEF |
| Experiment: | Western blot//Immunofluorescence//SA-β-gal activity assay |
| Description: | Compared to physioxia, hyperoxia promoted senescence and triggered activation of TGF-β signaling.Activation of TGF-β signaling by oxidative stress was accompanied by increased miR-29 accumulation and accelerated reduction in the abundance of total H4K20me3.Inhibition of TGF-β signaling by inhibitor treatment and Smad4 depletion diminished miR-29 expression, attenuated the reduction in Suv4-20h1 and Suv4-20h2 expression and produced partial recovery of H4K20me3. Moreover, alterations in TGF-β signaling changed the progression of senescence and specifically altered H4K20me3 without affecting other histone modifications. Disruption of TGF-β signaling by E-616452 restored H4K20me3 levels,attenuated SA-β-gal staining and enhanced the Mki67 signals in Suv4-20h-depleted cells, suggesting that H4K20me3 is a downstream effector of TGF-β signaling. In addition, after miR-29 was destroyed by miRNA inhibitors, activation of TGF-β signaling did not down-regulate Suv4-20h and H4K20me3. |
| Target gene: | MIR-29//H4K20ME3 |
| Official symbol(s): | MIR-29//H4K20ME3 |
| R-AG-Target gene: | Upregulation//Downregulation |
| Subcategory: | Unclear |
| Target gene experiment: | Western blot//qRT-PCR//SA-β-gal activity assay//Immunofluorescence |
| Target gene description: | We performed histone modifications scanning in senescent cells. The results showed that H4K20me1, -me2, and -me3 exhibited prominent down-regulation in senescent mouse embryonic fibroblasts (MEFs). Accordingly, the expression levels of Suv4-20h1 and Suv4-20h2, the two major methyltransferases mediating H4K20me3, were also decreased during senescence. Furthermore, depletion of Suv4-20h1, Suv4-20h2 or both (designated as Suv4-20h) by shRNAs and treatment with selective Suv4-20h inhibitor A-19636 led to reduced H4K20me3 protein abundance and premature senescence.Meanwhile, disruption of the TGF-β pathway by E-616452 treatment mitigated the increase in miR-29 abundance and progression of senescence in cells with ectopic miR-29. |
| Regulatory pathway: | -- |
| R-AG-Pathway: | -- |
| Pathway experiment: | -- |
| Pathway description: | -- |
Annotation:
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