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首页> 外文期刊>Molecular and Cellular Biology >Established epigenetic modifications determine the expression of developmentally regulated globin genes in somatic cell hybrids.
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Established epigenetic modifications determine the expression of developmentally regulated globin genes in somatic cell hybrids.

机译：建立的表观遗传修饰决定了体细胞杂种中发育调节的球蛋白基因的表达。

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Somatic cell hybrids generated from transgenic mouse cells have been used to examine the developmental regulation of human gamma-to-beta-globin gene switching. In hybrids between mouse erythroleukemia (MEL) cells and transgenic erythroblasts taken at various stages of development, there was regulated expression of the human fetal gamma and adult beta genes, reproducing the in vivo pattern prior to fusion. Hybrids formed from embryonic blood cells produced predominantly gamma mRNA, whereas beta gene expression was observed in adult hybrids and a complete range of intermediate patterns was found in fetal liver hybrids. The adult environment of the MEL cells, therefore, did not appear to influence selective transcription from this gene complex. Irradiation of the embryonic erythroid cells prior to fusion resulted in hybrids containing only small fragments of donor chromosomes, but the pattern of gene expression did not differ from that of unirradiated hybrids. This finding suggests that continued expression of trans-acting factors from the donor erythroblasts is not necessary for continued expression of the human gamma gene in MEL cells. These results contrast with the lack of developmental regulation of the cluster after transfection of naked DNA into MEL cells and suggest that epigenetic processes established during normal development result in the gene cluster adopting a developmental stage-specific, stable conformation which is maintained through multiple rounds of replication and transcription in the MEL cell hybrids. On prolonged culture, hybrids that initially expressed only the gamma transgene switched to beta gene expression. The time period of switching, from approximately 10 to > 40 weeks, was similar to that seen previously in human fetal erythroblast x MEL cell hybrids but in this case bore no relationship to the time of in vivo switching. It seems unlikely, therefore, that switching in these hybrids is regulated by a developmental clock.
机译：从转基因小鼠细胞生成的体细胞杂种已被用于检查人类γ-β-球蛋白基因转换的发育调控。在小鼠红血球（MEL）细胞和处于不同发育阶段的转基因成红细胞之间的杂种中，人类胎儿γ和成人β基因的表达受到调节，在融合前重现了体内模式。由胚胎血细胞形成的杂种主要产生γmRNA，而在成年杂种中观察到β基因表达，而在胎肝杂种中发现了完整范围的中间模式。因此，MEL细胞的成年环境似乎不影响该基因复合物的选择性转录。融合前对胚胎红系细胞的辐照导致杂交体仅含有供体染色体的小片段，但基因表达模式与未辐照的杂交体没有差异。该发现表明，对于来自人的γ基因在MEL细胞中的持续表达，来自供体成红细胞的反式作用因子的持续表达不是必需的。这些结果与裸DNA转染到MEL细胞后缺乏簇的发育调控相反，并且表明正常发育过程中建立的表观遗传过程导致基因簇采用发育阶段特异性，稳定的构象，并通过多轮杂交维持MEL细胞杂种中的复制和转录。在长时间的培养中，最初仅表达γ转基因的杂种转换为β基因表达。从大约10周到> 40周的转换时间段与以前在人类胎儿成红细胞x MEL细胞杂种中看到的时间段相似，但在这种情况下与体内转换时间没有关系。因此，这些杂种的切换似乎不太可能受到发育时钟的调节。

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