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Analysis of the DNA methylome and transcriptome in granulopoiesis reveals timed changes and dynamic enhancer methylation

Ronnerblad, Michelle; Andersson, Robin; Olofsson, Tor LU ; Douagi, Iyadh; Karimi, Mohsen; Lehmann, Soren; Hoof, Ilka; de Hoon, Michiel; Itoh, Masayoshi and Nagao-Sato, Sayaka, et al. (2014) In Blood 123(17). p.79-89
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... (More)
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. (Less)
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Blood
volume
123
issue
17
pages
79 - 89
publisher
American Society of Hematology
external identifiers
  • wos:000335895800004
  • scopus:84899660132
ISSN
1528-0020
DOI
10.1182/blood-2013-02-482893
language
English
LU publication?
yes
id
9925fbfc-e6a3-4e99-887d-5100b9c892a7 (old id 4470100)
date added to LUP
2014-07-01 07:40:46
date last changed
2017-10-22 03:02:10
@article{9925fbfc-e6a3-4e99-887d-5100b9c892a7,
  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.},
  author       = {Ronnerblad, Michelle and Andersson, Robin and Olofsson, Tor and Douagi, Iyadh and Karimi, Mohsen and Lehmann, Soren and Hoof, Ilka and de Hoon, Michiel and Itoh, Masayoshi and Nagao-Sato, Sayaka and Kawaji, Hideya and Lassmann, Timo and Carninci, Piero and Hayashizaki, Yoshihide and Forrest, Alistair R. R. and Sandelin, Albin and Ekwall, Karl and Arner, Erik and Lennartsson, Andreas},
  issn         = {1528-0020},
  language     = {eng},
  number       = {17},
  pages        = {79--89},
  publisher    = {American Society of Hematology},
  series       = {Blood},
  title        = {Analysis of the DNA methylome and transcriptome in granulopoiesis reveals timed changes and dynamic enhancer methylation},
  url          = {http://dx.doi.org/10.1182/blood-2013-02-482893},
  volume       = {123},
  year         = {2014},
}