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

作者：Ronnerblad Michelle; Andersson Robin; Olofsson Tor; Douagi Iyadh; Karimi Mohsen; Lehmann Soren; 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; Arner Erik; Lennartsson Andreas^*

来源：Blood, 2014, 123(17): E79-E89.

DOI：10.1182/blood-2013-02-482893

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.

• 出版日期2014-4-24