Zhang Fan, Pomerantz Jason H, Sen George, Palermo Adam T, Blau Helen M
Baxter Laboratory in Genetic Pharmacology, Departments of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305-3175, USA.
Proc Natl Acad Sci U S A. 2007 Mar 13;104(11):4395-400. doi: 10.1073/pnas.0700181104. Epub 2007 Mar 7.
DNA methylation is among the most stable epigenetic marks, ensuring tissue-specific gene expression in a heritable manner throughout development. Here we report that differentiated mesodermal somatic cells can confer tissue-specific changes in DNA methylation on epidermal progenitor cells after fusion in stable multinucleate heterokaryons. Myogenic factors alter regulatory regions of genes in keratinocyte cell nuclei, demethylating and activating a muscle-specific gene and methylating and silencing a keratinocyte-specific gene. Because these changes occur in the absence of DNA replication or cell division, they are mediated by an active mechanism. Thus, the capacity to transfer epigenetic changes to other nuclei is not limited to embryonic stem cells and oocytes but is also a property of highly specialized mammalian somatic cells. These results suggest the possibility of directing the reprogramming of readily available postnatal human progenitor cells toward specific tissue cell types.
DNA甲基化是最稳定的表观遗传标记之一，可确保在整个发育过程中以可遗传的方式实现组织特异性基因表达。我们在此报告，分化的中胚层体细胞在与稳定的多核异核体融合后，可将DNA甲基化的组织特异性变化赋予表皮祖细胞。成肌因子改变角质形成细胞核中基因的调控区域，使一个肌肉特异性基因去甲基化并激活，同时使一个角质形成细胞特异性基因甲基化并沉默。由于这些变化发生在没有DNA复制或细胞分裂的情况下，它们是由一种活跃机制介导的。因此，将表观遗传变化转移到其他细胞核的能力不仅限于胚胎干细胞和卵母细胞，也是高度特化的哺乳动物体细胞的特性。这些结果提示了将易于获得的出生后人类祖细胞重编程为特定组织细胞类型的可能性。
