PXD003915 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Analysis of HER2 genomic binding in breast cancer cells identifies a global role in direct gene regulation |
Description | HER2 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. |
HostingRepository | PRIDE |
AnnounceDate | 2024-10-22 |
AnnouncementXML | Submission_2024-10-22_05:04:37.638.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Aisling Redmond |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | No PTMs are included in the dataset |
Instrument | LTQ Orbitrap Velos |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2016-04-06 03:56:44 | ID requested | |
1 | 2020-05-26 11:06:09 | announced | |
⏵ 2 | 2024-10-22 05:04:38 | announced | 2024-10-22: 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 affiliation | University of Cambridge, Cancer Research UK Cambridge Institute, Li Ka Shing Centre, Cambridge, CB2 0RE, UK |
contact email | jason.carroll@cruk.cam.ac.uk |
lab head | |
Aisling Redmond |
contact affiliation | University of Cambridge |
contact email | aislingredmond@yahoo.com |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD003915
- Label: PRIDE project
- Name: Analysis of HER2 genomic binding in breast cancer cells identifies a global role in direct gene regulation