title: Distinct Trends of DNA Methylation Patterning in the Innate and Adaptive Immune Systems.
abstract: DNA methylation and the localization and post-translational modification of nucleosomes are interdependent factors that contribute to the generation of distinct phenotypes from genetically identical cells. With 112 whole-genome bisulfite sequencing datasets from the BLUEPRINT Epigenome Project, we analyzed the global development of DNA methylation patterns during lineage commitment and maturation of a range of immune system effector cells and the cancers that arise from them. We show clear trends in methylation patterns that are distinct in the innate and adaptive arms of the human immune system, both globally and in relation to consistently positioned nucleosomes. Most notable are a progressive loss of methylation in developing lymphocytes and the consistent occurrence of non-CG methylation in specific cell types. Cancer samples from the two lineages are further polarized, suggesting the involvement of distinct lineage-specific epigenetic mechanisms. We anticipate broad utility for this resource as a basis for further comparative epigenetic analyses.
authors.affiliation: CNAG-CRG, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST), Baldiri i Reixac 4, Barcelona 08028, Spain; Universitat Pompeu Fabra (UPF), Barcelona 08002, Spain.
authors.forename: Ronald P
authors.initials: RP
authors.lastname: Schuyler
authors.affiliation: CNAG-CRG, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST), Baldiri i Reixac 4, Barcelona 08028, Spain; Universitat Pompeu Fabra (UPF), Barcelona 08002, Spain.
authors.forename: Angelika
authors.initials: A
authors.lastname: Merkel
authors.affiliation: CNAG-CRG, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST), Baldiri i Reixac 4, Barcelona 08028, Spain; Universitat Pompeu Fabra (UPF), Barcelona 08002, Spain.
authors.forename: Emanuele
authors.initials: E
authors.lastname: Raineri
authors.affiliation: Dipartimento di Biochimica Biofisica e Patologia Generale, Seconda Università degli Studi di Napoli, Vico Luigi de Crecchio 7, Napoli 80138, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Altucci
authors.affiliation: Department of Hematology, University of Groningen and University Medical Center Groningen, PO Box 30001, 9700 RB Groningen, the Netherlands.
authors.forename: Edo
authors.initials: E
authors.lastname: Vellenga
authors.affiliation: Department of Molecular Biology, Radboud University, Faculty of Science, Nijmegen Centre for Molecular Life Sciences, 6500 HB Nijmegen, the Netherlands.
authors.forename: Joost H A
authors.initials: JHA
authors.lastname: Martens
authors.affiliation: Department of Blood Cell Research, Sanquin Research and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, Plesmanlaan 125, 1066 CX Amsterdam, the Netherlands.
authors.forename: Farzin
authors.initials: F
authors.lastname: Pourfarzad
authors.affiliation: Department of Blood Cell Research, Sanquin Research and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, Plesmanlaan 125, 1066 CX Amsterdam, the Netherlands; Emma Children's Hospital, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands.
authors.forename: Taco W
authors.initials: TW
authors.lastname: Kuijpers
authors.affiliation: Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Long Road, CB2 0PT Cambridge, UK; National Health Service (NHS) Blood and Transplant, Cambridge Biomedical Campus, Long Road, CB2 0PT Cambridge, UK.
authors.forename: Frances
authors.initials: F
authors.lastname: Burden
authors.affiliation: Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Long Road, CB2 0PT Cambridge, UK; National Health Service (NHS) Blood and Transplant, Cambridge Biomedical Campus, Long Road, CB2 0PT Cambridge, UK.
authors.forename: Samantha
authors.initials: S
authors.lastname: Farrow
authors.affiliation: Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Long Road, CB2 0PT Cambridge, UK; National Health Service (NHS) Blood and Transplant, Cambridge Biomedical Campus, Long Road, CB2 0PT Cambridge, UK.
authors.forename: Kate
authors.initials: K
authors.lastname: Downes
authors.affiliation: Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Long Road, CB2 0PT Cambridge, UK; National Health Service (NHS) Blood and Transplant, Cambridge Biomedical Campus, Long Road, CB2 0PT Cambridge, UK; British Heart Foundation Centre of Excellence, University of Cambridge, Cambridge Biomedical Campus, Long Road, CB2 0QQ Cambridge, UK; Department of Human Genetics, The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, CB10 1HH Cambridge, UK.
authors.forename: Willem H
authors.initials: WH
authors.lastname: Ouwehand
authors.affiliation: European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, CB10 1SD Cambridge, UK.
authors.forename: Laura
authors.initials: L
authors.lastname: Clarke
authors.affiliation: European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, CB10 1SD Cambridge, UK.
authors.forename: Avik
authors.initials: A
authors.lastname: Datta
authors.affiliation: European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, CB10 1SD Cambridge, UK.
authors.forename: Ernesto
authors.initials: E
authors.lastname: Lowy
authors.affiliation: European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, CB10 1SD Cambridge, UK.
authors.forename: Paul
authors.initials: P
authors.lastname: Flicek
authors.affiliation: Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Long Road, CB2 0PT Cambridge, UK; National Health Service (NHS) Blood and Transplant, Cambridge Biomedical Campus, Long Road, CB2 0PT Cambridge, UK; British Heart Foundation Centre of Excellence, University of Cambridge, Cambridge Biomedical Campus, Long Road, CB2 0QQ Cambridge, UK.
authors.forename: Mattia
authors.initials: M
authors.lastname: Frontini
authors.affiliation: Department of Molecular Biology, Radboud University, Faculty of Science, Nijmegen Centre for Molecular Life Sciences, 6500 HB Nijmegen, the Netherlands.
authors.forename: Hendrik G
authors.initials: HG
authors.lastname: Stunnenberg
authors.affiliation: Department of Anatomic Pathology, Pharmacology and Microbiology, University of Barcelona, Institut d'Investigacions Biomédiques August Pi i Sunyer (IDIBAPS), Barcelona 08036, Spain.
authors.forename: José I
authors.initials: JI
authors.lastname: Martín-Subero
authors.affiliation: CNAG-CRG, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST), Baldiri i Reixac 4, Barcelona 08028, Spain; Universitat Pompeu Fabra (UPF), Barcelona 08002, Spain.
authors.forename: Ivo
authors.initials: I
authors.lastname: Gut
authors.affiliation: CNAG-CRG, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST), Baldiri i Reixac 4, Barcelona 08028, Spain; Universitat Pompeu Fabra (UPF), Barcelona 08002, Spain. Electronic address: simon.heath@gmail.com.
authors.forename: Simon
authors.initials: S
authors.lastname: Heath
mesh_terms: D056704:Adaptive Immunity / Q000235:genetics*; D001402:B-Lymphocytes / Q000378:metabolism; D001483:Base Sequence; D001665:Binding Sites; D000076246:CCCTC-Binding Factor; D019175:DNA Methylation / Q000235:genetics*; D015226:Dinucleoside Phosphates / Q000235:genetics; D005091:Exons / Q000235:genetics; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics*; D008214:Lymphocytes / Q000378:metabolism; D022423:Myeloid Cells / Q000378:metabolism; D009707:Nucleosomes
chemical_list: D000076246:CCCTC-Binding Factor; D015226:Dinucleoside Phosphates; D009707:Nucleosomes; C015772:CpG dinucleotide
keywords: BLUEPRINT; CTCF; DNA methylation; epigenetics; hematopoiesis; nucleosomes; whole-genome bisulfite sequencing