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PXD029313

PXD029313 is an original dataset announced via ProteomeXchange.

Dataset Summary
Titlers143348853 in vitro DNA pulldown
DescriptionNon-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.
HostingRepositoryPRIDE
AnnounceDate2022-04-21
AnnouncementXMLSubmission_2022-04-21_01:30:52.872.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterGerard Llimos Aubach
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListNo PTMs are included in the dataset
InstrumentOrbitrap Fusion Lumos
Dataset History
RevisionDatetimeStatusChangeLog Entry
02021-10-25 00:03:22ID requested
12022-04-21 01:30:53announced
Publication List
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]
Keyword List
submitter keyword: rs143348853, DNA pulldown, genetic variant, indel
Contact List
Bart Deplancke
contact affiliationLaboratory of Systems Biology and Genetics, Institute of Bioengineering, School of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland
contact emailbart.deplancke@epfl.ch
lab head
Gerard Llimos Aubach
contact affiliationEPFL
contact emailgerardllimosaubach@gmail.com
dataset submitter
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