Biddle Adrian, Simeoni Ilenia, Gurdon J B
Wellcome Trust/Cancer Research UK Gurdon Institute, Cambridge, UK.
Development. 2009 Aug;136(16):2695-703. doi: 10.1242/dev.036327. Epub 2009 Jul 15.
Transplantation into eggs or oocytes is an effective means of achieving the reprogramming of somatic cell nuclei. We ask here whether the provision of gene-specific transcription factors forms part of the mechanism by which a gene that is repressed in somatic cells is transcribed in oocytes. We find that M1 oocytes have an extremely strong transcription-inducing activity. They cause muscle genes of nuclei from non-muscle somatic cells, after injection into oocytes, to be transcribed to nearly the same extent as muscle genes in muscle cells. We show, surprisingly, that the myogenic factor MyoD and other known myogenic factors are not required to induce the transcription of muscle genes in a range of non-muscle somatic cell nuclei after transplantation to Xenopus oocytes. The overexpression of Id, a dominant-negative repressor of MyoD, prevents maternal MyoD from binding to its consensus sequences; nevertheless, muscle genes are activated in somatic nuclei to the same extent as without Id. We conclude that M1 oocytes can reprogram somatic nuclei in a different way to other experimental procedures: oocytes do not suppress the transcription of inappropriate genes and they activate a gene without the help of its known transcription factors. We suggest that these characteristics might be a special property of amphibian oocytes, and possibly of oocytes in general.
移植到卵子或卵母细胞中是实现体细胞重编程的有效手段。我们在此探讨基因特异性转录因子的提供是否是体细胞中被抑制的基因在卵母细胞中得以转录的机制的一部分。我们发现M1卵母细胞具有极强的转录诱导活性。将非肌肉体细胞的细胞核注入卵母细胞后,它们能使这些细胞核中的肌肉基因转录,其程度几乎与肌肉细胞中的肌肉基因相同。令人惊讶的是,我们发现将一系列非肌肉体细胞的细胞核移植到非洲爪蟾卵母细胞后,诱导肌肉基因转录并不需要生肌因子MyoD和其他已知的生肌因子。Id是MyoD的显性负性抑制剂,其过表达会阻止母源性MyoD与其共有序列结合;然而,体细胞细胞核中的肌肉基因仍能被激活,且激活程度与未过表达Id时相同。我们得出结论,M1卵母细胞能够以一种与其他实验方法不同的方式对体细胞进行重编程:卵母细胞不会抑制不适当基因的转录,并且它们在没有已知转录因子帮助的情况下就能激活一个基因。我们认为这些特性可能是两栖类卵母细胞的特殊属性,也许一般卵母细胞都具有。