PXD025736

PXD025736 is an original dataset announced via ProteomeXchange.

Title	Dnmt1 has de novo activity targeted to transposable elements
Description	DNA methylation plays a critical role in development, particularly in repressing retrotransposons. The mammalian methylation landscape is dependent on the combined activities of the canonical maintenance enzyme Dnmt1 and the de novo Dnmts, 3a and 3b. Here we demonstrate that Dnmt1 displays de novo methylation activity in vitro and in vivo with specific retrotransposon targeting. We used whole-genome bisulfite and long-read Nanopore sequencing in genetically engineered methylation depleted embryonic stem cells to provide an in-depth assessment and quantification of this activity. Utilizing additional knockout lines and molecular characterization, we show that Dnmt1's de novo methylation activity depends on Uhrf1 and its genomic recruitment overlaps with targets that enrich for Trim28 and H3K9 trimethylation. Our data demonstrate that Dnmt1 can de novo add and maintain DNA methylation, especially at retrotransposons and that this mechanism may provide additional stability for long-term repression and epigenetic propagation throughout development.
HostingRepository	PRIDE
AnnounceDate	2021-06-29
AnnouncementXML	Submission_2021-06-29_08:51:43.859.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	David Meierhofer
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2021-04-30 03:19:06	ID requested
1	2021-06-29 00:22:02	announced
⏵ 2	2021-06-29 08:51:44	announced	2021-06-29: Updated project metadata.

10.1038/S41594-021-00603-8;

Haggerty C, Kretzmer H, Riemenschneider C, Kumar AS, Mattei AL, Bailly N, Gottfreund J, Giesselmann P, Weigert R, Br, ä, ndl B, Giehr P, Buschow R, Galonska C, von Meyenn F, Pappalardi MB, McCabe MT, Wittler L, Giesecke-Thiel C, Mielke T, Meierhofer D, Timmermann B, M, ü, ller FJ, Walter J, Meissner A, Dnmt1 has de novo activity targeted to transposable elements. Nat Struct Mol Biol, 28(7):594-603(2021) [pubmed]

submitter keyword: Dnmt1, Uhrf1, retrotransposon, DNA methylation

Alexander Meissner
contact affiliation	Department of Genome Regulation, Max Planck Institute for Molecular Genetics, Berlin, Germany
contact email	meissner@molgen.mpg.de
lab head
David Meierhofer
contact affiliation	Mass Spectrometry Facility MPIMG
contact email	meierhof@molgen.mpg.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/2021/06/PXD025736

PRIDE project URI

• PRIDE
  1. PXD025736
     1. Label: PRIDE project
     2. Name: Dnmt1 has de novo activity targeted to transposable elements