Department of Biosciences and Nutrition, Center for Biosciences, NOVUM, Karolinska Institutet, Stockholm, Sweden;
Blood. 2014 Apr 24;123(17):e79-89. doi: 10.1182/blood-2013-02-482893. Epub 2014 Mar 26.
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.
在发育过程中，表观遗传机制（如 DNA 甲基化）被认为提供了一种细胞记忆，以维持多能性，但也稳定细胞命运决定，并指导谱系限制。在这项研究中，我们着手描述在粒细胞生成过程中 DNA 甲基化和基因表达的变化，使用 4 个不同的细胞群体，从寡能的共同髓系祖细胞阶段到终末分化的中性粒细胞。我们观察到，在粒细胞生成过程中，差异甲基化位点（DMS）通常表现出甲基化程度降低。甲基化似乎在特定的分化阶段发生变化，并与关键造血转录因子的转录和活性变化重叠。DMS 优先位于远离 CpG 岛和海岸的区域。此外，DMS 在增强子元件中过度表达，并富集在分化过程中活跃的增强子中。总的来说，这项研究详细描述了粒细胞生成过程中发生的表观遗传和转录变化，并支持 DNA 甲基化作为血细胞分化的调节机制的作用。
