PXD019794

PXD019794 is an original dataset announced via ProteomeXchange.

Title	ChIP-MS of DPPA3/STELLA in mouse embryonic stem cells
Description	Genome-wide DNA demethylation is a unique feature of mammalian development and naïve pluripotent stem cells. So far, it was unclear how mammals specifically achieve global DNA hypomethylation, given the high conservation of the DNA (de-)methylation machinery among vertebrates. We found that DNA demethylation requires TET activity but mostly occurs at sites where TET proteins are not bound suggesting a rather indirect mechanism. Among the few specific genes bound and activated by TET proteins was the naïve pluripotency and germline marker Dppa3 (Pgc7, Stella), which undergoes TDG dependent demethylation. The requirement of TET proteins for genome-wide DNA demethylation could be bypassed by ectopic expression of Dppa3. We show that DPPA3 binds and displaces UHRF1 from chromatin and thereby prevents the recruitment and activation of the maintenance DNA methyltransferase DNMT1. We demonstrate that DPPA3 alone can drive global DNA demethylation when transferred to amphibians (Xenopus) and fish (medaka), both species that naturally do not have a Dppa3 gene and exhibit no post-fertilization DNA demethylation. Our results show that TET proteins are responsible for active and - indirectly also for - passive DNA demethylation; while TET proteins initiate local and gene-specific demethylation in vertebrates, the recent emergence of DPPA3 introduced a unique means of genome-wide passive demethylation in mammals and contributed to the evolution of epigenetic regulation during early mammalian development.
HostingRepository	PRIDE
AnnounceDate	2020-10-12
AnnouncementXML	Submission_2020-10-12_06:16:06.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	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2020-06-15 16:41:34	ID requested
⏵ 1	2020-10-12 06:16:07	announced

Dataset with its publication pending

submitter keyword: ESCs, epigenetics, ChIP-MS, DNA methylation

Michael Wierer
contact affiliation	Department of Proteomics and Signal Transduction, Max Planck Institute for Biochemistry, Martinsried, Germany
contact email	wierer@biochem.mpg.de
lab head
Enes Ugur
contact affiliation	Heinrich Leonhardt Lab, Department of Humanbiology & BioImaging, LMU Munich
contact email	ugur@bio.lmu.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD019794
     1. Label: PRIDE project
     2. Name: ChIP-MS of DPPA3/STELLA in mouse embryonic stem cells