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首页> 外文期刊>Journal of Molecular Biology >Mutant genetic background affects the functional rearrangement and kinetic properties of JMJD2b histone demethylase.
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Mutant genetic background affects the functional rearrangement and kinetic properties of JMJD2b histone demethylase.

机译：突变的遗传背景会影响JMJD2b组蛋白脱甲基酶的功能重排和动力学性质。

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摘要

We have studied JMJD2b histone demethylase, which antagonizes H3K9me3 in the pericentromeric heterochromatin. In cells with a deficiency in the histone methyltransferase SUV39h, the level of full-length JMJD2b (JMJD2b-GFP-1086) at chromocenters was reduced, corresponding to a global decrease in JMJD2b and H3K9me3. In wild-type fibroblasts, the chromatin of ribosomal genes, which is dense with H3K9 methylation, lacked JMJD2b-GFP-1086, while mutant and truncated forms of JMJD2b densely occupied the nucleolar compartment. This implies that the PHD Zn-fingers and Tudor domains, which were removed in truncated JMJD2b, are responsible for the aberrant JMJD2b function. Intriguingly, the JMJD2b-GFP-1086 level was significantly higher in tumor cell nucleoli. The kinetic properties of JMJD2b-GFP-1086 in the nucleoli and nucleoplasm of normal and tumor cells were similar; approximately 50% recovery of prebleached intensity was reached after <1 s. However, the mobile fraction of JMJD2b-GFP-1086 was increased in SUV39h-deficient cells. Similarly, the mobile fractions of mutant JMJD2b(1-424)H189A-GFP and truncated JMJD2b(1-424)GFP were greater than that measured for the full-length protein. We suggest that nucleoli are the site of an aberrant function of JMJD2b, the kinetic properties of which can be influenced by a mutant genetic background.
机译：我们已经研究了JMJD2b组蛋白脱甲基酶，它拮抗着丝粒异染色质中的H3K9me3。在组蛋白甲基转移酶SUV39h缺乏的细胞中，发色中心的全长JMJD2b（JMJD2b-GFP-1086）水平降低，相当于JMJD2b和H3K9me3总体下降。在野生型成纤维细胞中，富含H3K9甲基化的核糖体基因染色质缺乏JMJD2b-GFP-1086，而JMJD2b的突变体和截短形式则密集地占据了核仁区。这意味着在截断的JMJD2b中删除的PHD锌指和Tudor域负责异常的JMJD2b功能。有趣的是，肿瘤细胞核仁中的JMJD2b-GFP-1086水平明显更高。 JMJD2b-GFP-1086在正常细胞和肿瘤细胞的核仁和核质中的动力学特性相似。 <1 s后，达到约50％的预漂白强度恢复率。但是，JMJD2b-GFP-1086的移动部分在SUV39h缺陷细胞中增加。类似地，突变体JMJD2b（1-424）H189A-GFP和截短的JMJD2b（1-424）GFP的可移动部分大于全长蛋白质的可移动部分。我们建议核仁是JMJD2b异常功能的位点，其动力学特性可能会受到突变遗传背景的影响。

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