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@ARTICLE{Wang:298179,
author = {H. Wang$^*$ and A. A. Syed$^*$ and J. Krijgsveld$^*$ and G.
Sigismondo$^*$},
title = {{I}solation of proteins on chromatin (i{POC}) reveals
signaling pathway-dependent alterations in the {DNA}-bound
proteome.},
journal = {Molecular $\&$ cellular proteomics},
volume = {24},
number = {3},
issn = {1535-9476},
address = {Bethesda, Md.},
publisher = {The American Society for Biochemistry and Molecular
Biology},
reportid = {DKFZ-2025-00198},
pages = {100908},
year = {2025},
note = {#EA:B230#LA:B230# / Volume 24, Issue 3, March 2025, 100908},
abstract = {Signaling 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.},
keywords = {DNA-binding proteins (Other) / H3K27me3 (Other) /
PI3K/AKT/mTOR signaling pathway (Other) / PRC2 (Other) /
SUZ12 (Other) / cancer (Other) / chromatin (Other) /
chromatin dynamics (Other) / pathway inhibition (Other) /
polycomb (Other)},
cin = {B230},
ddc = {610},
cid = {I:(DE-He78)B230-20160331},
pnm = {312 - Funktionelle und strukturelle Genomforschung
(POF4-312)},
pid = {G:(DE-HGF)POF4-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:39842777},
doi = {10.1016/j.mcpro.2025.100908},
url = {https://inrepo02.dkfz.de/record/298179},
}