The Drosophila jumonji gene encodes a JmjC‐containing nuclear protein that is required for metamorphosis

The Drosophila jumonji gene encodes a JmjC‐containing nuclear protein that is required for metamorphosis
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DOI:
10.1111/j.1742-4658.2007.06135.x
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发表时间:
2007-12
期刊:
The FEBS Journal
影响因子:
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通讯作者:
N. Sasai;Yasuko Kato;Gaku Kimura;T. Takeuchi;M. Yamaguchi
N. Sasai;Yasuko Kato;Gaku Kimura;T. Takeuchi;M. Yamaguchi
中科院分区:
其他
文献类型:
--
作者:
N. Sasai;Yasuko Kato;Gaku Kimura;T. Takeuchi;M. Yamaguchi

文献摘要

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Jumonji(Jmj)是一种转录抑制因子,在抑制小鼠细胞增殖和各种组织发育中起重要作用。为了进一步阐明Jmj在发育过程中的作用,并深入了解Jmj介导的转录调控机制,我们利用果蝇作为模式生物。果蝇Jmj(dJmj)与哺乳动物Jmj在JmjN、JmjC和富含AT的相互作用结构域以及N末端阻遏结构域中具有高度同源性。dJmj定位于唾液腺多线染色体上的数百个常染色质位点,但不定位于染色中心异染色质。此外,dJmj被排除在Ser 5-磷酸化RNA聚合酶II抗体染色区域之外,表明dJmj在转录失活染色质中的功能。djmj的缺失导致幼虫和蛹致死,其表型与蜕皮激素调节基因突变体中观察到的表型相似,这意味着dJmj参与了蜕皮激素途径中基因表达的抑制。转基因小鼠Jmj大多与dJmj共定位,并部分挽救dJmj突变体的表型,表明dJmj是哺乳动物Jmj的功能同源物。此外,djmj的突变抑制了T(2;3)SbV重排的位置效应杂色。这些研究结果表明,dJmj控制发育重要基因的表达,通过修改染色质进入转录沉默状态。
Jumonji (Jmj) is a transcriptional repressor that plays important roles in the suppression of cell proliferation and development of various tissues in the mouse. To further clarify the roles of Jmj during development and gain insight into mechanisms of Jmj‐mediated transcriptional regulation, we have taken advantage of Drosophila as a model organism. Drosophila Jmj (dJmj) shares high homology with mammalian Jmj in the JmjN, JmjC and AT‐rich interaction domains, as well as in the N‐terminal repression domain. dJmj localizes to hundreds of euchromatic sites but not to chromocenter heterochromatin on salivary gland polytene chromosomes. In addition, dJmj is excluded from regions stained with an antibody against Ser5‐phosphorylated RNA polymerase II, suggesting a function of dJmj in transcriptionally inactive chromatin. Loss of djmj results in larval and pupal lethality with phenotypes similar to those observed in mutants of ecdysone‐regulated genes, implying the involvement of dJmj in the repression of gene expression in the ecdysone pathway. Transgenic mouse Jmj mostly colocalizes with dJmj and partially rescues the phenotypes of djmj mutants, indicating that dJmj is a functional homolog of mammalian Jmj. Furthermore, mutation in djmj suppresses position effect variegation of the T(2;3)SbV rearrangement. These findings suggest that dJmj controls expression of developmentally important genes through modification of chromatin into a transcriptionally silenced state.