Wen Duancheng, Banaszynski Laura A, Rosenwaks Zev, Allis C David, Rafii Shahin
a Ronald O. Perleman and Claudia Cohen Center for Reproductive Medicine; New York, NY USA.
Nucleus. 2014 Sep-Oct;5(5):369-75. doi: 10.4161/nucl.36231.
Transfer of a somatic nucleus into an enucleated oocyte is the most efficient approach for somatic cell reprogramming. While this process is known to involve extensive chromatin remodeling of the donor nucleus, the maternal factors responsible and the underlying chromatin-based mechanisms remain largely unknown. Here we discuss our recent findings demonstrating that the histone variant H3.3 plays an essential role in reprogramming and is required for reactivation of key pluripotency genes in somatic cell nuclear transfer (SCNT) embryos. Maternal-derived H3.3 replaces H3 in the donor nucleus shortly after oocyte activation, with the amount of replacement directly related to the differentiation status of the donor nucleus in SCNT embryos. We provide additional evidence to suggest that de novo synthesized H3.3 replaces histone H3 carrying repressive modifications in the donor nuclei of SCNT embryos, and hypothesize that replacement may occur at specific loci that must be reprogrammed for gene reactivation.
将体细胞核转移到去核卵母细胞中是体细胞重编程最有效的方法。虽然已知这一过程涉及供体细胞核广泛的染色质重塑，但负责的母体因子和潜在的基于染色质的机制在很大程度上仍然未知。在这里，我们讨论我们最近的发现，这些发现表明组蛋白变体H3.3在重编程中起关键作用，并且是体细胞核移植（SCNT）胚胎中关键多能性基因重新激活所必需的。卵母细胞激活后不久，母体来源的H3.3就会取代供体细胞核中的H3，其取代量与SCNT胚胎中供体细胞核的分化状态直接相关。我们提供了额外的证据表明，重新合成的H3.3取代了SCNT胚胎供体细胞核中带有抑制性修饰的组蛋白H3，并推测这种取代可能发生在特定的位点，这些位点必须进行重编程才能实现基因重新激活。
