DNA methylation dynamics during in vivo differentiation of blood and skin stem cells.

DNA methylation dynamics during in vivo differentiation of blood and skin stem cells.
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DOI:
10.1016/j.molcel.2012.06.019
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发表时间:
2012-08-24
期刊:
影响因子:
16
通讯作者:
Meissner, Alexander
Meissner, Alexander
中科院分区:
生物学1区
文献类型:
--
作者:
Bock, Christoph;Beerman, Isabel;Lien, Wen-Hui;Smith, Zachary D.;Gu, Hongcang;Boyle, Patrick;Gnirke, Andreas;Fuchs, Elaine;Rossi, Derrick J.;Meissner, Alexander

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DNA甲基化是所有脊椎动物共有的表观遗传调控机制。功能研究强调了其与组织稳态的相关性,但在体内分化过程中DNA甲基化的全球动态仍有待研究。在这里,我们报告了小鼠成体干细胞分化的高分辨率DNA甲基化图谱,重点是血液和皮肤谱系的19个纯化细胞群。DNA甲基化变化是位点特异性的,并且在幅度上相对温和。它们经常与谱系相关的转录因子及其结合位点重叠,表明DNA甲基化可能保护细胞免受异常转录因子激活的影响。DNA甲基化和基因表达提供了互补的信息,将两者结合起来使我们能够直接从基因组数据中推断出血液谱系的细胞分化层次。总之,这些结果表明,成体干细胞的体内分化与DNA甲基化的基因组分布中的小但信息丰富的变化相关。
DNA methylation is a mechanism of epigenetic regulation that is common to all vertebrates. Functional studies underscore its relevance for tissue homeostasis, but the global dynamics of DNA methylation during in vivo differentiation remain underexplored. Here we report high-resolution DNA methylation maps of adult stem cell differentiation in mouse, focusing on 19 purified cell populations of the blood and skin lineages. DNA methylation changes were locus-specific and relatively modest in magnitude. They frequently overlapped with lineage-associated transcription factors and their binding sites, suggesting that DNA methylation may protect cells from aberrant transcription factor activation. DNA methylation and gene expression provided complementary information, and combining the two enabled us to infer the cellular differentiation hierarchy of the blood lineage directly from genomic data. In summary, these results demonstrate that in vivo differentiation of adult stem cells is associated with small but informative changes in the genomic distribution of DNA methylation.
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