Dataset Information

Analysis of HER2 genomic binding in breast cancer cells identifies a global role in direct gene regulation

ABSTRACT: 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.

INSTRUMENT(S): LTQ Orbitrap Velos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

DISEASE(S): Breast Cancer

SUBMITTER: Aisling Redmond

LAB HEAD: Jason S Carroll

PROVIDER: PXD003915 | Pride | 2020-05-26

REPOSITORIES: pride

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Analysis of HER2 genomic binding in breast cancer cells identifies a global role in direct gene regulation.

Redmond Aisling M AM Omarjee Soleilmane S Chernukhin Igor I Le Romancer Muriel M Carroll Jason S JS

PloS one 20191120 11

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 two breast cancer cell lines. We find genome-wide re- ...[more]

PMID: 31747426

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			Action	DRS
	HER2_IP_chromatin_628.msf	Msf
	HER2_IP_chromatin_628.raw	Raw
	HER2_IP_nuclear_602.msf	Msf
	HER2_IP_nuclear_602.raw	Raw
	IgG_IP_chromatin_629.msf	Msf