Histone methylation controls telomerase-independent telomere lengthening in cells undergoing dedifferentiation
Histone methylation controls telomerase-independent telomere lengthening in cells undergoing dedifferentiation
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DOI：
10.1016/j.ydbio.2007.03.023
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发表时间：
2007-06-15
影响因子：
2.7
通讯作者：
Zemach, Assaf
中科院分区：
文献类型：
--
作者：
Grafi, Gideon;Ben-Meir, Hagit;Zemach, Assaf
细胞去分化是生物学中诸如再生和核克隆等热点问题的基础，并且在植物和动物中具有共同特征。在植物中，这一过程的特征是分化的叶细胞向原生质体（没有细胞壁的植物细胞）的转变，并伴随着与基因表达重编程相关的全局染色质重组。对增殖和愈伤组织形成缺陷突变体的筛选鉴定了kyp-2-编码组蛋白H3赖氨酸9（H3 K9）甲基转移酶的KRYPTONITE（KYP）/SUV H4基因中的突变体。端粒长度分析显示，在野生型，但不是在kyp-2原生质体端粒随机端粒酶无关的延长。在kyp-2突变体中，端粒重复序列不再与二甲基化H3 K9相关。拟南芥端粒酶逆转录酶（tert）突变体显示加速增殖，尽管它的端粒短，但它也显示加速细胞死亡。微阵列分析揭示了泛素蛋白水解系统的几个组成部分，与野生型原生质体相比，它们在kyp-2中下调。因此，我们的研究结果表明，组蛋白甲基化活性所需的建立/维持去分化状态和/或重新进入细胞周期，至少部分地，通过激活基因的产物参与泛素蛋白水解途径。此外，我们的研究结果阐明了细胞去分化的复杂性，特别是DNA重组的发生可能导致基因组不稳定。(c)2007爱思唯尔公司All rights reserved.
Cellular dedifferentiation underlies topical issues in biology such as regeneration and nuclear cloning and has common features in plants and animals. In plants, this process characterizes the transition of differentiated leaf cells to protoplasts (plant cells devoid of cell walls) and is accompanied by global chromatin reorganization associated with reprogramming of gene expression. A screen for mutants defective in proliferation and callus formation identified kyp-2-a mutant in the KRYPTONITE (KYP)/SUVH4 gene encoding a histone H3 lysine 9 (H3K9) methyltransferase. Analysis of telomere length revealed stochastic telomerase-independent lengthening of telomeres in wild type but not in kyp-2 protoplasts. In kyp-2 mutant, telomeric repeats were no longer associated with dimethylated H3K9. The Arabidopsis telomerase reverse transcriptase (tert) mutant displayed accelerated proliferation despite its short telomeres, though it also showed accelerated cell death. Microarray analysis uncovered several components of the ubiquitin proteolytic system, which are downregulated in kyp-2 compared to wild-type protoplasts. Thus, our results suggest that histone methylation activity is required for the establishment/maintenance of the dedifferentiated state and/or reentry into the cell cycle, at least partly, through activation of genes whose products are involved in the ubiquitin proteolytic pathway. In addition, our results illuminate the complexity of cellular dedifferentiation, particularly the occurrence of DNA recombination that can lead to genome instability. (c) 2007 Elsevier Inc. All rights reserved.