Mitosis gives a brief window of opportunity for a change in gene transcription.
Mitosis gives a brief window of opportunity for a change in gene transcription.
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DOI：
10.1371/journal.pbio.1001914
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发表时间：
2014-07
期刊：
影响因子：
9.8
通讯作者：
Gurdon J
中科院分区：
文献类型：
--
作者：
Halley-Stott RP;Jullien J;Pasque V;Gurdon J
在有丝分裂核移植实验中，许多基因的基因表达发生重大变化。这支持了有丝分裂在正常发育过程中促进新细胞命运决定的观点。细胞分化非常稳定，但可以通过体细胞核移植、细胞融合和iPS逆转。核移植到两栖类卵母细胞提供了一个特殊的机会，测试转录重编程没有细胞分裂。我们在这里表明，核移植到两栖类卵母细胞后，有丝分裂染色质的重编程速度比间期核快100倍。我们发现，当细胞经历有丝分裂时，它们的基因会经历一个对卵母细胞重编程因子（有丝分裂优势）异常高反应的临时阶段。有丝分裂优势不能用核穿透、DNA修饰、组蛋白乙酰化、磷酸化、甲基化或盐溶性染色体蛋白来解释。我们的研究结果表明，组蛋白H2A去泛素化可能占，至少部分，收购有丝分裂优势。他们支持的一般原则，细胞质因子在有丝分裂过程中暂时进入基因可能有助于体细胞核重编程和获得新的细胞命运在正常发育。细胞分裂非常活跃，在发展的时候，新的基因表达和新的细胞谱系出现。在有丝分裂中，大多数转录因子暂时从染色体上被置换。我们发现，移植到卵母细胞后，体细胞核已同步有丝分裂可以重编程多能性基因表达高达100倍，比间期核。我们发现，当细胞经历有丝分裂时，它们的基因会经历一个对卵母细胞重编程因子（有丝分裂优势）异常高反应的临时阶段。基因组中的许多其他基因也显示出有丝分裂优势，这影响转录增强的速率而不是最终水平。这归因于染色质状态，而不是重编程因子更快地通过核膜。有丝分裂时组蛋白H2A去泛素化是获得有丝分裂优势所必需的。我们的研究结果支持的一般原则，即在有丝分裂过程中的细胞质因子的临时访问基因促进体细胞核重编程和收购新的细胞命运在正常发育。
In mitotic nuclei transplant experiments, many genes undergo major changes in gene expression. This supports the idea that mitosis facilitates new cell fate decisions during normal development. Cell differentiation is remarkably stable but can be reversed by somatic cell nuclear transfer, cell fusion, and iPS. Nuclear transfer to amphibian oocytes provides a special opportunity to test transcriptional reprogramming without cell division. We show here that, after nuclear transfer to amphibian oocytes, mitotic chromatin is reprogrammed up to 100 times faster than interphase nuclei. We find that, as cells traverse mitosis, their genes pass through a temporary phase of unusually high responsiveness to oocyte reprogramming factors (mitotic advantage). Mitotic advantage is not explained by nuclear penetration, DNA modifications, histone acetylation, phosphorylation, methylation, nor by salt soluble chromosomal proteins. Our results suggest that histone H2A deubiquitination may account, at least in part, for the acquisition of mitotic advantage. They support the general principle that a temporary access of cytoplasmic factors to genes during mitosis may facilitate somatic cell nuclear reprogramming and the acquisition of new cell fates in normal development. Cells are dividing very actively at a time in development when new gene expression and new cell lineages arise. At mitosis, most transcription factors are temporarily displaced from chromosomes. We show that, after transplantation to oocytes, somatic cell nuclei that have been synchronized in mitosis can be reprogrammed to pluripotency gene expression up to 100 times faster than interphase nuclei. We find that, as cells traverse mitosis, their genes pass through a temporary phase of unusually high responsiveness to oocyte reprogramming factors (mitotic advantage). Many other genes in the genome have also shown a mitotic advantage, which affects the rate rather than the final level of transcriptional enhancement. This is attributable to a chromatin state rather than to more rapid passage of reprogramming factors through the nuclear membrane. Histone H2A deubiquitination at mitosis is required for the acquisition of mitotic advantage. Our results support the general principle that a temporary access of cytoplasmic factors to genes during mitosis facilitates somatic cell nuclear reprogramming and the acquisition of new cell fates in normal development.
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影响因子：
4.6
作者：
Egli, Dieter;Eggan, Kevin
通讯作者：
Eggan, Kevin
影响因子：
64.5
作者：
Tsubouchi T;Soza-Ried J;Brown K;Piccolo FM;Cantone I;Landeira D;Bagci H;Hochegger H;Merkenschlager M;Fisher AG
通讯作者：
Fisher AG
DOI：
10.1073/pnas.96.26.14984
发表时间：
1999-12-21
影响因子：
11.1
作者：
Wakayama, T;Rodriguez, I;Mombaerts, P
通讯作者：
Mombaerts, P
影响因子：
2.5
作者：
Oback, B.;Wells, D. N.
通讯作者：
Wells, D. N.
影响因子：
64.5
作者：
Lemaitre, JM;Danis, E;Méchali, M
通讯作者：
Méchali, M