PXD019438-1

PXD019438 is an original dataset announced via ProteomeXchange.

Title	TET2 is a component of the ER complex and controls 5mC to 5hmC conversion at ER cis-regulatory regions
Description	Estrogen receptor-alpha (ER) drives tumour development and metastasis in ER positive (ER+) breast cancer. GATA3 is a transcription factor that has been closely linked to ER function, but the role of GATA3 in ER-transcriptional activity is not clear. We sought to identify the contribution of GATA3 to the ER complex, by conducting quantitative multiplexed rapid immunoprecipitation mass spectrometry of endogenous proteins (qPLEX-RIME), to assess changes to the ER complex in response to GATA3 depletion. Unexpectedly, very few proteins were dissociated from the ER complex in the absence of GATA3, with the only major change being loss of TET2 in the ER complex. In breast cancer cells and Patient-Derived Xenograft (PDX) tissue, TET2 binding events were shown to constitute a near-total subset of ER binding events, and loss of TET2 was functionally associated with reduced activation of proliferative pathways. To investigate the TET2-ER relationship, the role of TET2 in regulating DNA modifications in ER+ breast cancer cells was examined. TET2 knockdown did not appear to result in changes to global DNA methylation, however, oxidation of methylated DNA to 5-hydroxymethylcytosine (5hmC) was significantly reduced after TET2 depletion and these events occurred at ER enhancers. These findings implicate TET2 in the production and maintenance of 5hmC at ER sites, providing a potential mechanism for TET2-mediated regulation of ER target genes.
HostingRepository	PRIDE
AnnounceDate	2021-02-10
AnnouncementXML	Submission_2021-02-10_12:59:49.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Evangelia Papachristou
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	methylthiolated residue; monohydroxylated residue; deamidated residue
Instrument	Orbitrap Fusion Lumos; LTQ Orbitrap Velos

Revision	Datetime	Status	ChangeLog Entry
0	2020-05-28 01:51:26	ID requested
⏵ 1	2021-02-10 12:59:50	announced
2	2024-10-22 05:18:51	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

submitter keyword: TET2, qPLEX-RIME, Estrogen receptor alpha, breast cancer

Jason Carroll
contact affiliation	Senior group Leader
contact email	Jason.Carroll@cruk.cam.ac.uk
lab head
Evangelia Papachristou
contact affiliation	Senior Scientific Assistant
contact email	Eva.Papachristou@cruk.cam.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD019438
     1. Label: PRIDE project
     2. Name: TET2 is a component of the ER complex and controls 5mC to 5hmC conversion at ER cis-regulatory regions