PXD028566-1

PXD028566 is an original dataset announced via ProteomeXchange.

Title	Dissection of TET1 catalytic and non-catalytic functions reveals DNA demethylation independent gene and ERV regulation
Description	Surveillance of DNA methylation in mammals is critical for genome stability and epigenetic regulation. The discovery of the ten-eleven translocation (TET) proteins catalyzing the oxidation from 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC) revolutionized the understanding of DNA methylation dynamics. Interestingly, in recent years evidence accumulated that TET1 also harbours non-catalytic functions. However, the role and mechanism of TET1 DNA demethylation independent functions still remain poorly understood. Here, we use genome engineering and quantitative multi-omics approaches to dissect the non-catalytic role of TET1. Strikingly, we find that the majority of transcriptional regulation depends on non-catalytic functions of TET1. To gain insights into possible mechanisms by which TET1 regulates transcription independent of DNA demethylation, we asked if the loss of TET1 is accompanied by changes in the histone modificaiton landscape. To this end, we compared the relative abundances of core histone modifications between Tet1 KO, Tet1 CM and WT mESCs using quantitative LC-MS/MS analysis. Surprisingly, we observed a profound global reduction of pH4Kac and H4K20me3 as well as H3K27me3 in Tet1 KO mESC. Vice versa, the monomethylation states of the latter two residues, H3K27me1 and H4K20me1 were significantly increased in Tet1 KO. Similar to the results from the transcriptome data, most of these changes were specific to Tet1 KO cells.
HostingRepository	PRIDE
AnnounceDate	2024-10-07
AnnouncementXML	Submission_2024-10-07_13:42:43.109.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Andrey Tvardovskiy
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	monomethylated residue; acetylated residue; dimethylated residue; N6,N6,N6-trimethyl-L-lysine
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2021-09-16 07:40:49	ID requested
⏵ 1	2024-10-07 13:42:43	announced
2	2024-10-22 05:38:49	announced	2024-10-22: Updated project metadata.

10.1093/NAR/GKAC642;

submitter keyword: methylation, acetylation,TET1, histone PTMs

Sebastian Bultmann
contact affiliation	Department of Biology II and Center for Molecular Biosystems (BioSysM), Human Biology and BioImaging, Ludwig-Maximilians-Universität München, Munich 81377, Germany
contact email	bultmann@biologie.uni-muenchen.de
lab head
Andrey Tvardovskiy
contact affiliation	Institute of Functional Epigenetics, Helmholtz Zentrum München, Neuherberg 85764, Germany
contact email	andrey.tvardovskiy@helmholtz-muenchen.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/2022/08/PXD028566

PRIDE project URI

• PRIDE
  1. PXD028566
     1. Label: PRIDE project
     2. Name: Dissection of TET1 catalytic and non-catalytic functions reveals DNA demethylation independent gene and ERV regulation