PXD019514-1

PXD019514 is an original dataset announced via ProteomeXchange.

Title	Distinct and stage-specific contributions of TET1 and TET2 to stepwise cytosine oxidation in the transition from naive to primed pluripotency
Description	Cytosine DNA bases can be methylated by DNA methyltransferases and subsequently oxidized by TET proteins. The resulting 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC) are considered demethylation intermediates as well as stable epigenetic marks. To dissect the contribution of these cytosine modifying enzymes, we generated combinations of Tet knockout (KO) embryonic stem cells (ESCs) and systematically measured protein and DNA modification levels at the transition from naive to primed pluripotency. Whereas the increase of genomic 5-methylcytosine (5mC) levels during exit from pluripotency correlated with an upregulation of the de novo DNA methyltransferases DNMT3A and DNMT3B, the subsequent oxidation steps turned out to be far more complex. The strong increase of oxidized cytosine bases (5hmC, 5fC, and 5caC) was accompanied by a drop in TET2 levels, yet the analysis of KO cells suggested that TET2 is responsible for most 5fC formation. The comparison of modified cytosine and enzyme levels in Tet KO cells revealed distinct and differentiation-dependent contributions of TET1 and TET2 to 5hmC and 5fC formation arguing against a processive mechanism of 5mC oxidation. The apparent independent steps of 5hmC and 5fC formation suggest yet to be identified mechanisms regulating TET activity and may constitute another layer of epigenetic regulation.
HostingRepository	PRIDE
AnnounceDate	2020-07-24
AnnouncementXML	Submission_2020-07-23_23:06:17.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Enes Ugur
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	monohydroxylated residue; acetylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2020-06-02 01:25:11	ID requested
⏵ 1	2020-07-23 23:06:18	announced
2	2024-10-22 05:09:52	announced	2024-10-22: Updated project metadata.

Mulholland CB, Traube FR, Ugur E, Parsa E, Eckl EM, Sch, ö, nung M, Modic M, Bartoschek MD, Stolz P, Ryan J, Carell T, Leonhardt H, Bultmann S, Distinct and stage-specific contributions of TET1 and TET2 to stepwise cytosine oxidation in the transition from naive to primed pluripotency. Sci Rep, 10(1):12066(2020) [pubmed]

submitter keyword: mouse embryonic stem cells, epiblast-like cells, epigenetics, DNA methylation

Sebastian Bultmann
contact affiliation	Department of Biology II and Center for Integrated Protein Science Munich (CIPSM), Ludwig-Maximilians-Universität München, Planegg-Martinsried, Germany
contact email	bultmann@bio.lmu.de
lab head
Enes Ugur
contact affiliation	Heinrich Leonhardt Lab, Department of Humanbiology & BioImaging, LMU Munich
contact email	ugur@bio.lmu.de
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/2020/07/PXD019514

PRIDE project URI

• PRIDE
  1. PXD019514
     1. Label: PRIDE project
     2. Name: Distinct and stage-specific contributions of TET1 and TET2 to stepwise cytosine oxidation in the transition from naive to primed pluripotency