title: Analysis of the DNA methylome and transcriptome in granulopoiesis reveals timed changes and dynamic enhancer methylation.
abstract: In development, epigenetic mechanisms such as DNA methylation have been suggested to provide a cellular memory to maintain multipotency but also stabilize cell fate decisions and direct lineage restriction. In this study, we set out to characterize changes in DNA methylation and gene expression during granulopoiesis using 4 distinct cell populations ranging from the oligopotent common myeloid progenitor stage to terminally differentiated neutrophils. We observed that differentially methylated sites (DMSs) generally show decreased methylation during granulopoiesis. Methylation appears to change at specific differentiation stages and overlap with changes in transcription and activity of key hematopoietic transcription factors. DMSs were preferentially located in areas distal to CpG islands and shores. Also, DMSs were overrepresented in enhancer elements and enriched in enhancers that become active during differentiation. Overall, this study depicts in detail the epigenetic and transcriptional changes that occur during granulopoiesis and supports the role of DNA methylation as a regulatory mechanism in blood cell differentiation.
authors.affiliation: Department of Biosciences and Nutrition, Center for Biosciences, NOVUM, Karolinska Institutet, Stockholm, Sweden;
authors.forename: Michelle
authors.initials: M
authors.lastname: Rönnerblad
authors.forename: Robin
authors.initials: R
authors.lastname: Andersson
authors.forename: Tor
authors.initials: T
authors.lastname: Olofsson
authors.forename: Iyadh
authors.initials: I
authors.lastname: Douagi
authors.forename: Mohsen
authors.initials: M
authors.lastname: Karimi
authors.forename: Sören
authors.initials: S
authors.lastname: Lehmann
authors.forename: Ilka
authors.initials: I
authors.lastname: Hoof
authors.forename: Michiel
authors.initials: M
authors.lastname: de Hoon
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Itoh
authors.forename: Sayaka
authors.initials: S
authors.lastname: Nagao-Sato
authors.forename: Hideya
authors.initials: H
authors.lastname: Kawaji
authors.forename: Timo
authors.initials: T
authors.lastname: Lassmann
authors.forename: Piero
authors.initials: P
authors.lastname: Carninci
authors.forename: Yoshihide
authors.initials: Y
authors.lastname: Hayashizaki
authors.forename: Alistair R R
authors.initials: AR
authors.lastname: Forrest
authors.forename: Albin
authors.initials: A
authors.lastname: Sandelin
authors.forename: Karl
authors.initials: K
authors.lastname: Ekwall
authors.forename: Erik
authors.initials: E
authors.lastname: Arner
authors.forename: Andreas
authors.initials: A
authors.lastname: Lennartsson
mesh_terms: D002454:Cell Differentiation; D002469:Cell Separation; D018899:CpG Islands; D003596:Cytosine / Q000378:metabolism; D019175:DNA Methylation; D004742:Enhancer Elements, Genetic; D044127:Epigenesis, Genetic; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D023281:Genomics; D006098:Granulocytes / Q000166:cytology*; D006801:Humans; D009504:Neutrophils / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D012313:RNA / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology; D014157:Transcription Factors / Q000378:metabolism; D059467:Transcriptome
chemical_list: D014157:Transcription Factors; D012313:RNA; D003596:Cytosine