PXD029313

PXD029313 is an original dataset announced via ProteomeXchange.

Title	rs143348853 in vitro DNA pulldown
Description	Non-coding variants coordinate transcription factor (TF) binding and chromatin mark enrichment changes over regions spanning >100 kb. We named these molecularly coordinated regions “variable chromatin modules” (VCMs), providing a conceptual framework of how regulatory variation might shape complex traits. To better understand the molecular mechanisms underlying VCM formation, here, we mechanistically dissect an uncharacterized VCM-modulating non-coding variant that is associated with reduced chronic lymphocytic leukemia (CLL) predisposition and disease progression. This common, germline variant constitutes a 5-bp indel that controls the activity of an AXIN2 gene-linked VCM by creating a MEF2 binding site, which, upon binding, activates a super-enhancer-like regulatory element. This triggers a big change in TF binding activity and chromatin state at an enhancer cluster spanning >150 kb, coinciding with long-range chromatin compaction and AXIN2 up-regulation. Our results support a model in which the indel acts as an AXIN2 VCM-activating TF nucleation event, which modulates CLL pathology.
HostingRepository	PRIDE
AnnounceDate	2022-04-21
AnnouncementXML	Submission_2022-04-21_01:30:52.872.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Gerard Llimos Aubach
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2021-10-25 00:03:22	ID requested
⏵ 1	2022-04-21 01:30:53	announced

Llimos G, Gardeux V, Koch U, Kribelbauer JF, Hafner A, Alpern D, Pezoldt J, Litovchenko M, Russeil J, Dainese R, Moia R, Mahmoud AM, Rossi D, Gaidano G, Plass C, Lutsik P, Gerhauser C, Waszak SM, Boettiger A, Radtke F, Deplancke B, A leukemia-protective germline variant mediates chromatin module formation via transcription factor nucleation. Nat Commun, 13(1):2042(2022) [pubmed]

submitter keyword: rs143348853, DNA pulldown, genetic variant, indel

Bart Deplancke
contact affiliation	Laboratory of Systems Biology and Genetics, Institute of Bioengineering, School of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland
contact email	bart.deplancke@epfl.ch
lab head
Gerard Llimos Aubach
contact affiliation	EPFL
contact email	gerardllimosaubach@gmail.com
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/2022/04/PXD029313

PRIDE project URI

• PRIDE
  1. PXD029313
     1. Label: PRIDE project
     2. Name: rs143348853 in vitro DNA pulldown