Nature Communications (Apr 2022)
A leukemia-protective germline variant mediates chromatin module formation via transcription factor nucleation
- Gerard Llimos,
- Vincent Gardeux,
- Ute Koch,
- Judith F. Kribelbauer,
- Antonina Hafner,
- Daniel Alpern,
- Joern Pezoldt,
- Maria Litovchenko,
- Julie Russeil,
- Riccardo Dainese,
- Riccardo Moia,
- Abdurraouf Mokhtar Mahmoud,
- Davide Rossi,
- Gianluca Gaidano,
- Christoph Plass,
- Pavlo Lutsik,
- Clarissa Gerhauser,
- Sebastian M. Waszak,
- Alistair Boettiger,
- Freddy Radtke,
- Bart Deplancke
Affiliations
- Gerard Llimos
- Institute of Bioengineering, School of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL)
- Vincent Gardeux
- Institute of Bioengineering, School of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL)
- Ute Koch
- Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences École Polytechnique Fédérale de Lausanne (EPFL)
- Judith F. Kribelbauer
- Institute of Bioengineering, School of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL)
- Antonina Hafner
- Department of Developmental Biology, Stanford University
- Daniel Alpern
- Institute of Bioengineering, School of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL)
- Joern Pezoldt
- Institute of Bioengineering, School of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL)
- Maria Litovchenko
- Institute of Bioengineering, School of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL)
- Julie Russeil
- Institute of Bioengineering, School of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL)
- Riccardo Dainese
- Institute of Bioengineering, School of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL)
- Riccardo Moia
- Division of Hematology, Department of Translational Medicine, University of Eastern Piedmont
- Abdurraouf Mokhtar Mahmoud
- Division of Hematology, Department of Translational Medicine, University of Eastern Piedmont
- Davide Rossi
- Oncology Institute of Southern Switzerland, Università della Svizzera italiana
- Gianluca Gaidano
- Division of Hematology, Department of Translational Medicine, University of Eastern Piedmont
- Christoph Plass
- Division of Epigenomics and Cancer Risk Factors, German Cancer Research Center (DKFZ)
- Pavlo Lutsik
- Division of Epigenomics and Cancer Risk Factors, German Cancer Research Center (DKFZ)
- Clarissa Gerhauser
- Division of Epigenomics and Cancer Risk Factors, German Cancer Research Center (DKFZ)
- Sebastian M. Waszak
- Centre for Molecular Medicine Norway (NCMM), Nordic EMBL Partnership, University of Oslo and Oslo University Hospital
- Alistair Boettiger
- Department of Developmental Biology, Stanford University
- Freddy Radtke
- Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences École Polytechnique Fédérale de Lausanne (EPFL)
- Bart Deplancke
- Institute of Bioengineering, School of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL)
- DOI
- https://doi.org/10.1038/s41467-022-29625-6
- Journal volume & issue
-
Vol. 13,
no. 1
pp. 1 – 21
Abstract
Non-coding variants can regulate transcription factor binding and gene expression at variable chromatin modules. Here, the authors show that a germline variant induces transcription factor nucleation through chromatin compaction leading to AXIN2 up-regulation and is associated to better prognosis in chronic lymphocytic leukaemia.
