PXD003915

PXD003915 is an original dataset announced via ProteomeXchange.

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

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.

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]

curator keyword: Biomedical

submitter keyword: breast cancer, RIME,HER2

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

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2020/05/PXD003915

PRIDE project URI

• PRIDE
  1. PXD003915
     1. Label: PRIDE project
     2. Name: Analysis of HER2 genomic binding in breast cancer cells identifies a global role in direct gene regulation