ORCID Profile
0000-0002-8459-7048
Current Organisations
The Alan Turing Institute
,
University of York
,
Universtiy of Cambridge
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Publisher: Springer Science and Business Media LLC
Date: 13-06-2018
DOI: 10.1038/S41467-018-04619-5
Abstract: Understanding the dynamics of endogenous protein–protein interactions in complex networks is pivotal in deciphering disease mechanisms. To enable the in-depth analysis of protein interactions in chromatin-associated protein complexes, we have previously developed a method termed RIME (Rapid Immunoprecipitation Mass spectrometry of Endogenous proteins). Here, we present a quantitative multiplexed method (qPLEX-RIME), which integrates RIME with isobaric labelling and tribrid mass spectrometry for the study of protein interactome dynamics in a quantitative fashion with increased sensitivity. Using the qPLEX-RIME method, we delineate the temporal changes of the Estrogen Receptor alpha (ERα) interactome in breast cancer cells treated with 4-hydroxytamoxifen. Furthermore, we identify endogenous ERα-associated proteins in human Patient-Derived Xenograft tumours and in primary human breast cancer clinical tissue. Our results demonstrate that the combination of RIME with isobaric labelling offers a powerful tool for the in-depth and quantitative characterisation of protein interactome dynamics, which is applicable to clinical s les.
Publisher: Cold Spring Harbor Laboratory
Date: 16-02-2018
DOI: 10.1101/266908
Abstract: VULCAN infers regulatory interactions of transcription factors by overlaying networks generated from tumor expression data onto ChIP-seq data. VULCAN analysis of estrogen receptor (ER) activation in breast cancer highlighted key components of the ER complex alongside a novel interaction with GRHL2. We demonstrate that GRHL2 is recruited to a subset of ER binding sites and regulates the transcriptional output of ER, as evidenced by: changes in ER-associated eRNA expression and stronger ER binding at active enhancers (H3K27ac sites) after GRHL2 knockdown. Our findings provide new insight into ER signaling and demonstrate VULCAN, available from Bioconductor, as a powerful predictive tool.
Publisher: Springer Science and Business Media LLC
Date: 13-05-2019
Publisher: Springer Science and Business Media LLC
Date: 14-06-2019
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Andrew N Holding.