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PXD003915

PXD003915 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleAnalysis of HER2 genomic binding in breast cancer cells identifies a global role in direct gene regulation
DescriptionHER2 is a transmembrane receptor tyrosine kinase, which plays a key role in breast cancer due to a common genomic amplification. It is used as a marker to stratify patients in the clinic and is targeted by a number of drugs including Trastuzumab and Lapatinib. HER2 has previously been shown to translocate to the nucleus. In this study, we have explored the properties of nuclear HER2 by analysing the binding of this protein to the chromatin in three breast cancer cell lines. We find genome-wide re-programming of HER2 binding after treatment with the growth factor EGF. Over 4,000 HER2 binding sites are found in all three breast cancer cell lines, and these occur near genes involved in protein kinase activity and signal transduction. HER2 was shown to co-localise at a subset of regions demarcated by H3K4me1, a hallmark of functional enhancer elements and HER2/H3K4me1 co-bound regions were enriched near EGF regulated genes providing evidence for their functional role as regulatory elements. A chromatin bound role for HER2 was verified by independent methods, including Proximity Ligation Assay (PLA), which confirmed a close association between HER2 and H3K4me1. Interestingly, HER2 bound to the ErbB2 gene itself indicating a potential self-regulatory mechanism for HER2. Mass spectrometry analysis of the chromatin bound HER2 complex identified EGFR and STAT3 as interacting partners. These findings reveal a global role for HER2 as a chromatin-associated factor that binds to enhancer elements to elicit direct gene expression events in breast cancer cells.
HostingRepositoryPRIDE
AnnounceDate2024-10-22
AnnouncementXMLSubmission_2024-10-22_05:04:37.638.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterAisling Redmond
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListNo PTMs are included in the dataset
InstrumentLTQ Orbitrap Velos
Dataset History
RevisionDatetimeStatusChangeLog Entry
02016-04-06 03:56:44ID requested
12020-05-26 11:06:09announced
22024-10-22 05:04:38announced2024-10-22: Updated project metadata.
Publication List
10.1371/journal.pone.0225180;
Redmond AM, Omarjee S, Chernukhin I, Le Romancer M, Carroll JS, Analysis of HER2 genomic binding in breast cancer cells identifies a global role in direct gene regulation. PLoS One, 14(11):e0225180(2019) [pubmed]
Keyword List
curator keyword: Biomedical
submitter keyword: breast cancer, RIME,HER2
Contact List
Jason S Carroll
contact affiliationUniversity of Cambridge, Cancer Research UK Cambridge Institute, Li Ka Shing Centre, Cambridge, CB2 0RE, UK
contact emailjason.carroll@cruk.cam.ac.uk
lab head
Aisling Redmond
contact affiliationUniversity of Cambridge
contact emailaislingredmond@yahoo.com
dataset submitter
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Dataset FTP location
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PRIDE project URI
Repository Record List
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