Department of Medicine, Division of Hematology, University of Washington, NE Pacific St, Box 357710, Seattle, WA 98195, USA.
Stem Cell Rev Rep. 2013 Aug;9(4):397-407. doi: 10.1007/s12015-012-9355-x.
Human embryonic stem cells provide an alternative to using human embryos for studying developmentally regulated gene expression. The co-expression of high levels of embryonic ε and fetal γ globin by the hESC-derived erythroblasts allows the interrogation of ε globin regulation at the transcriptional and epigenetic level which could only be attained previously by studying cell lines or transgenic mice. In this study, we compared the histone modifications across the β globin locus of the undifferentiated hESCs and hESC-, FL-, and mobilized PB CD34(+) cells-derived erythroblasts, which have distinct globin expression patterns corresponding to their developmental stages. We demonstrated that the histone codes employed by the β globin locus are conserved throughout development. Furthermore, in spite of the close proximity of the ε globin promoter, as compared to the β or γ globin promoter, with the LCR, a chromatin loop was also formed between the LCR and the active ε globin promoter, similar to the loop that forms between the β or γ globin promoters and the LCR, in contrary to the previously proposed tracking mechanism.
人类胚胎干细胞为研究发育调控基因表达提供了替代使用人类胚胎的方法。由 hESC 衍生的红细胞中高水平共表达的胚胎 ε 和胎儿 γ 珠蛋白，使得可以在转录和表观遗传水平上对 ε 珠蛋白的调控进行研究，而这以前只能通过研究细胞系或转基因小鼠来实现。在这项研究中，我们比较了未分化的 hESC 和 hESC-、FL-和动员 PB CD34(+)细胞衍生的红细胞中β 珠蛋白基因座的组蛋白修饰，这些细胞具有与其发育阶段相对应的不同的珠蛋白表达模式。我们证明了β 珠蛋白基因座所采用的组蛋白编码在整个发育过程中是保守的。此外，尽管 ε 珠蛋白启动子与 LCR 的距离与 β 或 γ 珠蛋白启动子相比非常接近，但在 LCR 和活性 ε 珠蛋白启动子之间也形成了一个染色质环，类似于在 β 或 γ 珠蛋白启动子和 LCR 之间形成的环，与之前提出的跟踪机制相反。
