TY - JOUR
T1 - Analysis of the DNA methylome and transcriptome in granulopoiesis reveals timed changes and dynamic enhancer methylation
AU - Ronnerblad, Michelle
AU - Andersson, Robin
AU - Olofsson, Tor
AU - Douagi, Iyadh
AU - Karimi, Mohsen
AU - Lehmann, Soren
AU - Hoof, Ilka
AU - de Hoon, Michiel
AU - Itoh, Masayoshi
AU - Nagao-Sato, Sayaka
AU - Kawaji, Hideya
AU - Lassmann, Timo
AU - Carninci, Piero
AU - Hayashizaki, Yoshihide
AU - Forrest, Alistair R. R.
AU - Sandelin, Albin
AU - Ekwall, Karl
AU - Arner, Erik
AU - Lennartsson, Andreas
PY - 2014
Y1 - 2014
N2 - 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.
AB - 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.
U2 - 10.1182/blood-2013-02-482893
DO - 10.1182/blood-2013-02-482893
M3 - Article
C2 - 24671952
SN - 1528-0020
VL - 123
SP - E79-E89
JO - Blood
JF - Blood
IS - 17
ER -