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000298179 1001_ $$0P:(DE-He78)a8e5fdea05628e1193d53792c5b99fbd$$aWang, Huiyu$$b0$$eFirst author
000298179 245__ $$aIsolation of proteins on chromatin (iPOC) reveals signaling pathway-dependent alterations in the DNA-bound proteome.
000298179 260__ $$aBethesda, Md.$$bThe American Society for Biochemistry and Molecular Biology$$c2025
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000298179 500__ $$a#EA:B230#LA:B230# / Volume 24, Issue 3, March 2025, 100908
000298179 520__ $$aSignaling pathways often convergence on transcription factors (TFs) and other DNA-binding proteins (DBPs) that regulate chromatin structure and gene expression, thereby governing a broad range of essential cellular functions. However, the repertoire of DBPs is incompletely understood even for the best-characterized pathways. Here, we optimized a strategy for the isolation of Proteins on Chromatin (iPOC) exploiting tagged nucleoside analogues to label the DNA and capture associated proteins, thus enabling the comprehensive, sensitive, and unbiased characterization of the DNA-bound proteome. We then applied iPOC to investigate chromatome changes upon perturbation of the cancer-relevant PI3K/AKT/mTOR pathway. Our results show distinct dynamics of the DNA-bound proteome upon selective inhibition of PI3K, AKT, or mTOR, and we provide evidence how this signaling cascade regulates the DNA-bound status of SUZ12, thereby modulating H3K27me3 levels. Collectively, iPOC is a powerful approach to study the composition of the DNA-bound proteome operating downstream of signaling cascades, thereby both expanding our knowledge of the mechanism of action of the pathway, and unveiling novel chromatin modulators that can potentially be targeted pharmacologically.
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000298179 650_7 $$2Other$$aDNA-binding proteins
000298179 650_7 $$2Other$$aH3K27me3
000298179 650_7 $$2Other$$aPI3K/AKT/mTOR signaling pathway
000298179 650_7 $$2Other$$aPRC2
000298179 650_7 $$2Other$$aSUZ12
000298179 650_7 $$2Other$$acancer
000298179 650_7 $$2Other$$achromatin
000298179 650_7 $$2Other$$achromatin dynamics
000298179 650_7 $$2Other$$apathway inhibition
000298179 650_7 $$2Other$$apolycomb
000298179 7001_ $$0P:(DE-HGF)0$$aSyed, Azmal Ali$$b1
000298179 7001_ $$0P:(DE-He78)939d5891259c638c1ab053b1456a578c$$aKrijgsveld, Jeroen$$b2$$udkfz
000298179 7001_ $$0P:(DE-He78)a63bd9276ca497fcfcd476478727a6dc$$aSigismondo, Gianluca$$b3$$eLast author$$udkfz
000298179 773__ $$0PERI:(DE-600)2071375-7$$a10.1016/j.mcpro.2025.100908$$gp. 100908 -$$n3$$p100908$$tMolecular & cellular proteomics$$v24$$x1535-9476$$y2025
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