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

Michelle Rönnerblad; Robin Andersson; Tor Olofsson; Iyadh Douagi; Mohsen Karimi; Sören Lehmann; Ilka Hoof; Michiel de Hoon; Masayoshi Itoh; Sayaka Nagao-Sato; Hideya Kawaji; Timo Lassmann; Piero Carninci; Yoshihide Hayashizaki; Alistair R R Forrest; Albin Gustav Sandelin; Karl Ekwall; Erik Arner; Andreas Lennartsson

doi:10.1182/blood-2013-02-482893

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

Michelle Rönnerblad, Robin Andersson, Tor Olofsson, Iyadh Douagi, Mohsen Karimi, Sören Lehmann, Ilka Hoof, Michiel de Hoon, Masayoshi Itoh, Sayaka Nagao-Sato, Hideya Kawaji, Timo Lassmann, Piero Carninci, Yoshihide Hayashizaki, Alistair R R Forrest, Albin Gustav Sandelin, Karl Ekwall, Erik Arner, Andreas Lennartsson

Bioinformatik og RNA Biologi

52 Citationer (Scopus)

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.

Originalsprog	Engelsk
Tidsskrift	Blood
Vol/bind	123
Udgave nummer	17
ISSN	0006-4971
DOI	https://doi.org/10.1182/blood-2013-02-482893
Status	Udgivet - 24 apr. 2014

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10.1182/blood-2013-02-482893

http://www.bloodjournal.org/content/bloodjournal/123/17/e79.full.pdf

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Rönnerblad, M., Andersson, R., Olofsson, T., Douagi, I., Karimi, M., Lehmann, S., Hoof, I., de Hoon, M., Itoh, M., Nagao-Sato, S., Kawaji, H., Lassmann, T., Carninci, P., Hayashizaki, Y., Forrest, A. R. R., Sandelin, A. G., Ekwall, K., Arner, E., & Lennartsson, A. (2014). Analysis of the DNA methylome and transcriptome in granulopoiesis reveal timed changes and dynamic enhancer methylation. Blood, 123(17). https://doi.org/10.1182/blood-2013-02-482893

Rönnerblad, M, Andersson, R, Olofsson, T, Douagi, I, Karimi, M, Lehmann, S, Hoof, I, de Hoon, M, Itoh, M, Nagao-Sato, S, Kawaji, H, Lassmann, T, Carninci, P, Hayashizaki, Y, Forrest, ARR, Sandelin, AG, Ekwall, K, Arner, E & Lennartsson, A 2014, 'Analysis of the DNA methylome and transcriptome in granulopoiesis reveal timed changes and dynamic enhancer methylation', Blood, bind 123, nr. 17. https://doi.org/10.1182/blood-2013-02-482893

@article{11ea832b8e8b447daa41d8a44e4b6604,

title = "Analysis of the DNA methylome and transcriptome in granulopoiesis reveal 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.",

author = "Michelle R{\"o}nnerblad and Robin Andersson and Tor Olofsson and Iyadh Douagi and Mohsen Karimi and S{\"o}ren Lehmann and Ilka Hoof and {de Hoon}, Michiel and Masayoshi Itoh and Sayaka Nagao-Sato and Hideya Kawaji and Timo Lassmann and Piero Carninci and Yoshihide Hayashizaki and Forrest, {Alistair R R} and Sandelin, {Albin Gustav} and Karl Ekwall and Erik Arner and Andreas Lennartsson",

year = "2014",

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day = "24",

doi = "10.1182/blood-2013-02-482893",

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TY - JOUR

T1 - Analysis of the DNA methylome and transcriptome in granulopoiesis reveal timed changes and dynamic enhancer methylation

AU - Rönnerblad, Michelle

AU - Andersson, Robin

AU - Olofsson, Tor

AU - Douagi, Iyadh

AU - Karimi, Mohsen

AU - Lehmann, Sören

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 Gustav

AU - Ekwall, Karl

AU - Arner, Erik

AU - Lennartsson, Andreas

PY - 2014/4/24

Y1 - 2014/4/24

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 - Journal article

C2 - 24671952

SN - 0006-4971

VL - 123

JO - Blood

JF - Blood

IS - 17

ER -

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

Abstract

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