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1000
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Abstract/Summary
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Phase separation, a biophysical segregation of subcellular milieus referred as condensates, is known to regulate
transcription, but its impacts on physiological processes are less clear. Here, we demonstrate the formation of liquidlike nuclear condensates by SGF29, a component of the SAGA transcriptional coactivator complex, during cellular
senescence in human mesenchymal progenitor cells (hMPCs) and fibroblasts. The Arg 207 within the intrinsically
disordered region is identified as the key amino acid residue for SGF29 to form phase separation. Through epigenomic
and transcriptomic analysis, our data indicated that both condensate formation and H3K4me3 binding of SGF29 are
essential for establishing its precise chromatin location, recruiting transcriptional factors and co-activators to target
specific genomic loci, and initiating the expression of genes associated with senescence, such as CDKN1A. The
formation of SGF29 condensates alone, however, may not be sufficient to drive H3K4me3 binding or achieve
transactivation functions. Our study establishes a link between phase separation and aging regulation, highlighting
nuclear condensates as a functional unit that facilitate shaping transcriptional landscapes in aging.
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