PXD013507

PXD013507 is an original dataset announced via ProteomeXchange.

Title	Modeling of DNA methylation in cis reveals principles of chromatin folding in vivo in the absence of crosslinking and ligation
Description	Mammalian chromosomes are folded into intricate hierarchies of interaction domains, within which topologically associating domains (TADs) and CTCF-associated loops partition the physical interactions between regulatory sequences. Current understanding of chromosome folding largely relies on chromosome conformation capture (3C)-based experiments, where chromosomal interactions are detected as ligation products after crosslinking of chromatin. To measure chromosome structure in vivo, quantitatively and without relying on crosslinking and ligation, we have implemented a modified version of damID named damC. DamC combines DNA-methylation based detection of chromosomal interactions with next-generation sequencing and a biophysical model of methylation kinetics. DamC performed in mouse embryonic stem cells provides the first in vivo validation of the existence of TADs and CTCF loops and confirms 3C-based measurements of the scaling of contact probabilities. Combining damC with transposon-mediated genomic engineering shows that new loops can be formed between ectopically introduced and endogenous CTCF sites, which alters the partitioning of physical interactions within TADs. This orthogonal approach to 3C provides the first crosslinking- and ligation-free validation of the existence of key structural features of mammalian chromosomes and provides novel insights into how chromosome structure within TADs can be manipulated.
HostingRepository	PRIDE
AnnounceDate	2019-06-03
AnnouncementXML	Submission_2019-06-03_07:56:11.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Vytautas Iesmantavicius
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2019-04-15 07:26:43	ID requested
1	2019-06-03 05:20:44	announced
⏵ 2	2019-06-03 07:56:12	announced	Updated project metadata.

Redolfi J, Zhan Y, Valdes-Quezada C, Kryzhanovska M, Guerreiro I, Iesmantavicius V, Pollex T, Grand RS, Mulugeta E, Kind J, Tiana G, Smallwood SA, de Laat W, Giorgetti L, DamC reveals principles of chromatin folding in vivo without crosslinking and ligation. Nat Struct Mol Biol, 26(6):471-480(2019) [pubmed]

curator keyword: Biological

submitter keyword: topologically associating domains, TADs, chromosome folding, chromosomal interactions, mouse embryonic stem cells, CTCF-associated loops, proteomic ruler

Luca Giorgetti
contact affiliation	Friedrich Miescher Institute for Biomedical Research Maulbeerstrasse 66 4058 Basel Switzerland
contact email	luca.giorgetti@fmi.ch
lab head
Vytautas Iesmantavicius
contact affiliation	Friedrich Miescher Institute for Biomedical Research
contact email	vytautas.iesmantavicius@fmi.ch
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/2019/06/PXD013507

PRIDE project URI

• PRIDE
  1. PXD013507
     1. Label: PRIDE project
     2. Name: Modeling of DNA methylation in cis reveals principles of chromatin folding in vivo in the absence of crosslinking and ligation