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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >A multistep mechanism for the activation of rearrangement in the immune system
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A multistep mechanism for the activation of rearrangement in the immune system

机译:激活免疫系统重排的多步机制

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摘要

Rearrangement of immune receptor loci is a developmentally controlled process that takes place exclusively in lymphoid cells. We have used a stable transfection system in pre-B cells to show that DNA methylation brings about histone underacetylation, histone H3(K9) methylation, DNasel resistance, and strong inhibition of both transcription and recombination. Strikingly, this repression is maintained in dividing cells even after removal of the original methyl groups responsible for its establishment, but in this state, rearrangement can now be induced by reacetylation of local histones using the drug Trichostatin A. This same combination of demethylation and histone acetylation is also required to activate germline transcription and recombination from the endogeneous kappa locus in vivo. These results indicate that the regulation of rearrangement is carried out by a multilayered synergistic process. [References: 46]
机译:免疫受体基因座的重排是发育控制的过程,仅在淋巴样细胞中发生。我们已经在pre-B细胞中使用了稳定的转染系统,以显示DNA甲基化带来组蛋白欠乙酰化,组蛋白H3(K9)甲基化,DNasel抗性以及对转录和重组的强烈抑制。令人惊讶的是,即使在去除负责其建立的原始甲基之后,这种阻抑作用仍维持在分裂细胞中,但是在这种状态下,现在可以通过使用药物曲妥他汀A对局部组蛋白进行重新乙酰化来诱导重排。脱甲基化和组蛋白的这种相同组合在体内激活内源性κ位点的种系转录和重组也需要乙酰化。这些结果表明,重排的调节是通过多层协同过程进行的。 [参考:46]

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