Proteomics

Dataset Information

0

Rs143348853 in vitro DNA pulldown


ABSTRACT: 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.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): B Cell, Cell Culture

SUBMITTER: Gerard Llimos Aubach  

LAB HEAD: Bart Deplancke

PROVIDER: PXD029313 | Pride | 2022-04-21

REPOSITORIES: Pride

Dataset's files

Source:
Action DRS
GLA_200702_Lumos_HpH_01.raw Raw
GLA_200702_Lumos_HpH_02.raw Raw
GLA_200702_Lumos_HpH_03.raw Raw
GLA_200702_Lumos_HpH_04.raw Raw
GLA_200702_Lumos_HpH_05.raw Raw
Items per page:
1 - 5 of 10
altmetric image

Publications


Non-coding variants coordinate transcription factor (TF) binding and chromatin mark enrichment changes over regions spanning >100 kb. These molecularly coordinated regions are named "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 a VCM-modulating noncoding variant that is associated with reduced chronic lymphocytic  ...[more]

Similar Datasets

2022-02-08 | GSE162387 | GEO
| EGAS00001002073 | EGA
| phs001704 | dbGaP
2019-09-03 | PXD014631 | Pride
| EGAS00001002518 | EGA
2014-09-29 | E-GEOD-53999 | biostudies-arrayexpress
2024-09-05 | PXD050685 | Pride
2024-09-10 | GSE276513 | GEO
2024-09-10 | GSE276515 | GEO
2024-09-10 | GSE276514 | GEO