ERG phase separation attenuates cellular senescence
Lu Pu, Zhiliang Zuo, Hui Zheng, Rui Ou, Ru Gao, Zhaomin Deng, Xiaochu Wu, Chun Xiao, Meiling Ge, Lixing Zhou, Haoran Jin, Shaochong Qi, Fengjuan Hu, Jieli Chen, Hang Li, Yan Zhao, Birong Dong, Hao Jiang
TL;DR
The study finds that ERG protein phase separation in centenarians' cells may help delay aging by reducing senescence-related gene activity.
Contribution
ERG phase separation is newly identified as a mechanism linking chromatin organization to cellular aging in centenarians.
Findings
Centenarians' PBMCs show unique chromatin accessibility patterns.
ERG phase separation reduces CDKN2A expression and senescence.
ERG condensates alter chromatin organization and aging phenotypes.
Abstract
Centenarians, individuals who reach extreme old age, provide a valuable model for understanding mechanisms associated with healthy aging. Using ATAC-seq and transcriptomic profiling of peripheral blood mononuclear cells from centenarians, we identified a distinct chromatin accessibility landscape linked to exceptional longevity. Integrative analysis highlighted the E-26 transformation-specific (ETS)-related transcription factor ERG as a longevity-associated regulator. Functional studies in human cells showed that ERG forms nuclear condensates through liquid-liquid phase separation, a property associated with altered chromatin organization and reduced expression of senescence-related genes, including CDKN2A. Consistent with these effects, ERG condensation was associated with attenuation of cellular senescence phenotypes. Together, these findings connect epigenomic features observed in…
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Taxonomy
TopicsTelomeres, Telomerase, and Senescence · Genetics, Aging, and Longevity in Model Organisms · Genomics and Chromatin Dynamics