{"ID": "PMID:35440565", "lab": {"title": "Deplancke Lab", "@id": "/labs/bart-deplancke-lab/", "correspondence": [{"contact_email": "IGJhcnQuZGVwbGFuY2tlQGVwZmwuY2g=", "@id": "/users/a1a6b714-436a-4bb7-9f7b-4d9fe6cac9be/", "display_title": "Bart Deplancke"}], "uuid": "d111721a-0880-4795-a5d5-835e3c318769", "status": "current", "@type": ["Lab", "Item"], "display_title": "Deplancke Lab", "pi": {"error": "no view permissions"}, "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin", "role.lab_submitter", "submits_for.d111721a-0880-4795-a5d5-835e3c318769"]}}, "url": "https://www.ncbi.nlm.nih.gov/pubmed/35440565", "award": {"status": "current", "description": "Funding source is from outside 4DN.", "@type": ["Award", "Item"], "project": "External", "name": "external-award", "uuid": "12a92962-8265-4fc0-b2f8-cf14f05db58b", "@id": "/awards/external-award/", "center": "External", "display_title": "EXTERNAL AWARD", "center_title": "External", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "title": "A leukemia-protective germline variant mediates chromatin module formation via  transcription factor nucleation.", "status": "current", "aliases": ["bart-deplancke-lab:deplancke_2018_llcs"], "authors": ["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"], "journal": "Nature communications", "abstract": "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 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  large change in TF binding activity and chromatin state at an enhancer cluster  spanning >150 kb, coinciding with subtle, long-range chromatin compaction and  robust 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.", "date_created": "2025-07-08T14:40:29.201733+00:00", "published_by": "External", "submitted_by": {"error": "no view permissions"}, "last_modified": {"modified_by": {"error": "no view permissions"}, "date_modified": "2025-07-08T17:59:19.962058+00:00"}, "date_published": "2022-04-19", "public_release": "2025-07-08", "schema_version": "2", "project_release": "2025-07-08", "exp_sets_prod_in_pub": [{"uuid": "13165dd3-956d-4244-b509-a5319a19b41f", "status": "released", "@type": ["ExperimentSetReplicate", "ExperimentSet", "Item"], "@id": "/experiment-set-replicates/4DNESFAJCG4W/", "experimentset_type": "replicate", "display_title": "4DNESFAJCG4W", "accession": "4DNESFAJCG4W", "experiments_in_set": [{"display_title": "multiplexed FISH on B-lymphocyte - 4DNEX1MX8Y7L", "status": "released", "@type": ["ExperimentMic", "Experiment", "Item"], "@id": "/experiments-mic/4DNEX1MX8Y7L/", "uuid": "e7a1ef05-fb7b-4914-9753-4f0f586cfd68", "experiment_type": {"@id": "/experiment-types/multiplexed-fish/", "display_title": "multiplexed FISH", "uuid": "bcdda46a-489d-4d22-be80-c9c21552c915", "title": "multiplexed FISH", "status": "released", "@type": ["ExperimentType", "Item"], "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, {"display_title": "multiplexed FISH on B-lymphocyte - 4DNEX5ICQCRY", "status": "released", "@type": ["ExperimentMic", "Experiment", "Item"], "@id": "/experiments-mic/4DNEX5ICQCRY/", "uuid": "b61ee99e-ed3c-4b41-923c-3a0a66cd1be1", "experiment_type": {"@id": "/experiment-types/multiplexed-fish/", "display_title": "multiplexed FISH", "uuid": "bcdda46a-489d-4d22-be80-c9c21552c915", "title": "multiplexed FISH", "status": "released", "@type": ["ExperimentType", "Item"], "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}], "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, {"uuid": "a45807cd-0e25-4f3c-97dc-48e748c755be", "status": "released", "@type": ["ExperimentSetReplicate", "ExperimentSet", "Item"], "@id": "/experiment-set-replicates/4DNESYNKYXQN/", "experimentset_type": "replicate", "display_title": "4DNESYNKYXQN", "accession": "4DNESYNKYXQN", "experiments_in_set": [{"display_title": "multiplexed FISH on B-lymphocyte - 4DNEXU2FYC2S", "status": "released", "@type": ["ExperimentMic", "Experiment", "Item"], "@id": "/experiments-mic/4DNEXU2FYC2S/", "uuid": "43732727-1d9b-4d52-b5ab-b8d80ad9a5af", "experiment_type": {"@id": "/experiment-types/multiplexed-fish/", "display_title": "multiplexed FISH", "uuid": "bcdda46a-489d-4d22-be80-c9c21552c915", "title": "multiplexed FISH", "status": "released", "@type": ["ExperimentType", "Item"], "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, {"display_title": "multiplexed FISH on B-lymphocyte - 4DNEX4L5AR91", "status": "released", "@type": ["ExperimentMic", "Experiment", "Item"], "@id": "/experiments-mic/4DNEX4L5AR91/", "uuid": "98937440-b294-4ad5-abd1-c715e64012fd", "experiment_type": {"@id": "/experiment-types/multiplexed-fish/", "display_title": "multiplexed FISH", "uuid": "bcdda46a-489d-4d22-be80-c9c21552c915", "title": "multiplexed FISH", "status": "released", "@type": ["ExperimentType", "Item"], "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}], "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}], "@id": "/publications/b87c4200-5443-460f-9f1c-2f8092c7cafb/", "@type": ["Publication", "Item"], "uuid": "b87c4200-5443-460f-9f1c-2f8092c7cafb", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}, "display_title": "Llimos G et al. 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