Dynamic DNA methylation reveals novel cis-regulatory elements in mouse hematopoiesis.

Autor: Schönung M; Section Translational Cancer Epigenomics, Division of Translational Medical Oncology, German Cancer Research Center and National Center for Tumor Diseases, Heidelberg, Germany; Faculty of Biosciences, Heidelberg University, Heidelberg, Germany., Hartmann M; Section Translational Cancer Epigenomics, Division of Translational Medical Oncology, German Cancer Research Center and National Center for Tumor Diseases, Heidelberg, Germany; Division of Pediatric Hematology and Oncology, Department of Pediatrics and Adolescent Medicine, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany., Krämer S; Section Translational Cancer Epigenomics, Division of Translational Medical Oncology, German Cancer Research Center and National Center for Tumor Diseases, Heidelberg, Germany; Faculty of Biosciences, Heidelberg University, Heidelberg, Germany; Biomedical Informatics, Data Mining and Data Analytics, Faculty of Applied Computer Science and Medical Faculty, University of Augsburg, Augsburg, Germany., Stäble S; Section Translational Cancer Epigenomics, Division of Translational Medical Oncology, German Cancer Research Center and National Center for Tumor Diseases, Heidelberg, Germany., Hakobyan M; Section Translational Cancer Epigenomics, Division of Translational Medical Oncology, German Cancer Research Center and National Center for Tumor Diseases, Heidelberg, Germany; Faculty of Biosciences, Heidelberg University, Heidelberg, Germany., Kleinert E; Section Translational Cancer Epigenomics, Division of Translational Medical Oncology, German Cancer Research Center and National Center for Tumor Diseases, Heidelberg, Germany., Aurich T; Division of Experimental Hematology, German Cancer Research Center, Heidelberg, Germany; Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), Heidelberg, Germany., Cobanoglu D; Section Translational Cancer Epigenomics, Division of Translational Medical Oncology, German Cancer Research Center and National Center for Tumor Diseases, Heidelberg, Germany; Institute of Pharmacy and Molecular Biotechnology, Heidelberg University, Heidelberg, Germany., Heidel FH; Innere Medizin C, Universitätsmedizin Greifswald, Greifswald, Germany; Leibniz Institute on Aging, Fritz-Lipmann-Institute, Jena, Germany., Fröhling S; Division of Translational Medical Oncology, German Cancer Research Center and National Center for Tumor Diseases, Heidelberg, Germany., Milsom MD; Division of Experimental Hematology, German Cancer Research Center, Heidelberg, Germany; Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), Heidelberg, Germany., Schlesner M; Biomedical Informatics, Data Mining and Data Analytics, Faculty of Applied Computer Science and Medical Faculty, University of Augsburg, Augsburg, Germany., Lutsik P; Division of Cancer Epigenomics, German Cancer Research Center, Heidelberg, Germany. Electronic address: p.lutsik@dkfz.de., Lipka DB; Section Translational Cancer Epigenomics, Division of Translational Medical Oncology, German Cancer Research Center and National Center for Tumor Diseases, Heidelberg, Germany; Faculty of Medicine, Otto-von-Guericke-University, Magdeburg, Germany. Electronic address: d.lipka@dkfz.de.
Jazyk: angličtina
Zdroj: Experimental hematology [Exp Hematol] 2023 Jan; Vol. 117, pp. 24-42.e7. Date of Electronic Publication: 2022 Nov 08.
DOI: 10.1016/j.exphem.2022.11.001
Abstrakt: Differentiation of hematopoietic stem and progenitor cells to terminally differentiated immune cells is accompanied by large-scale remodeling of the DNA methylation landscape. Although significant insights into the molecular mechanisms of hematopoietic tissue regeneration were derived from mouse models, profiling of DNA methylation has been hampered by high cost or low resolution using available methods. The recent development of the Infinium Mouse Methylation BeadChip (MMBC) array facilitates methylation profiling of the mouse genome at a single CpG resolution at affordable cost. We extended the RnBeads package to provide a computational framework for the analysis of MMBC data. This framework was applied to a newly generated reference map of mouse hematopoiesis encompassing nine different cell types. Analysis of dynamically regulated CpG sites showed progressive and unidirectional DNA methylation changes from hematopoietic stem and progenitor cells to differentiated hematopoietic cells and allowed the identification of lineage- and cell type-specific DNA methylation programs. Comparison with previously published catalogs of cis-regulatory elements (CREs) revealed 12,856 novel putative CREs that were dynamically regulated by DNA methylation (mdCREs). These mdCREs were predominantly associated with patterns of cell type-specific DNA hypomethylation and could be identified as epigenetic control regions regulating the expression of key hematopoietic genes during differentiation. In summary, we established an analysis pipeline for MMBC data sets and provide a DNA methylation atlas of mouse hematopoiesis. This resource allowed us to identify novel putative CREs involved in hematopoiesis and will serve as a platform to study epigenetic regulation of normal and malignant hematopoiesis.
Competing Interests: Conflict of Interest Disclosure The authors do not have any conflicts of interests to declare in relation to this work.
(Copyright © 2022 ISEH -- Society for Hematology and Stem Cells. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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