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

Rönnerblad, Michelle, Andersson, Robin, Olofsson, Tor, Douagi, Iyadh, Karimi, Mohsen, Lehmann, Sören, Hoof, Ilka, de Hoon, Michiel, Itoh, Masayoshi, Nagao-Sato, Sayaka, Kawaji, Hideya, Lassmann, Timo, Carninci, Piero, Hayashizaki, Yoshihide, Forrest, Alistair R. R., Sandelin, Albin, Ekwall, Karl, Amer, Erik, Lennartsson, Andreas, for the FANTOM consortium, Wells, Christine, Wolvetang, Ernst, Blumenthal, Antje, Kenna, Tony, Hitchens, Kelly, Ovchinnikov, Dmitry, Fearnley, Liam, Le Cao, Kim-Anh, Mason, Elizabeth, Nielsen, Lars and Vijayan, Dipti (2014) Analysis of the DNA methylome and transcriptome in granulopoiesis reveals timed changes and dynamic enhancer methylation. Blood, 123 17: e79-e89. doi:10.1182/blood-2013-02-482893

Author Rönnerblad, Michelle
Andersson, Robin
Olofsson, Tor
Douagi, Iyadh
Karimi, Mohsen
Lehmann, Sören
Hoof, Ilka
de Hoon, Michiel
Itoh, Masayoshi
Nagao-Sato, Sayaka
Kawaji, Hideya
Lassmann, Timo
Carninci, Piero
Hayashizaki, Yoshihide
Forrest, Alistair R. R.
Sandelin, Albin
Ekwall, Karl
Amer, Erik
Lennartsson, Andreas
for the FANTOM consortium
Wells, Christine
Wolvetang, Ernst
Blumenthal, Antje
Kenna, Tony
Hitchens, Kelly
Ovchinnikov, Dmitry
Fearnley, Liam
Le Cao, Kim-Anh
Mason, Elizabeth
Nielsen, Lars
Vijayan, Dipti
Title Analysis of the DNA methylome and transcriptome in granulopoiesis reveals timed changes and dynamic enhancer methylation
Journal name Blood   Check publisher's open access policy
ISSN 0006-4971
Publication date 2014-04-24
Sub-type Article (original research)
DOI 10.1182/blood-2013-02-482893
Open Access Status DOI
Volume 123
Issue 17
Start page e79
End page e89
Total pages 11
Place of publication Washington, DC, United States
Publisher American Society of Hematology
Language eng
Formatted abstract
Key Points
• In granulopoiesis, changes in DNA methylation preferably occur at points of lineage restriction in low CpG areas.
• DNA methylation is dynamic in enhancer elements and appears to regulate the expression of key transcription factors and neutrophil genes.

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.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ
Additional Notes Published FANTOM authors are "for the FANTOM consortium".

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Created: Fri, 27 Jun 2014, 00:38:52 EST by Cathy Fouhy on behalf of Institute for Molecular Bioscience