Comparing and Contrasting the Effects of Drosophila Condensin II Subunit dCAP-D3 Overexpression and Depletion in Vivo.
Comparing and Contrasting the Effects of Drosophila Condensin II Subunit dCAP-D3 Overexpression and Depletion in Vivo.
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DOI：
10.1534/genetics.118.301344
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发表时间：
2018-10
期刊：
影响因子：
3.3
通讯作者：
Longworth MS
中科院分区：
文献类型：
--
作者：
Deutschman E;Ward JR;Ho-A-Lim KT;Alban TJ;Zhang D;Willard B;Lemieux ME;Lathia JD;Longworth MS
凝缩蛋白II复合体在整个细胞周期的基因组组织和基因表达调控中起着重要的保守作用。先前的研究已将凝血素II亚基表达降低与多种疾病联系起来。在这里，我们发现在体细胞癌症中检测到凝缩素II亚基水平升高。为了评估凝血素II水平升高的潜在生物学效应，我们在黑腹果蝇幼虫组织中过表达凝血素II亚基dCAP-D3，并研究了凝血素II对有丝分裂和期间特异性功能的影响。有趣的是，虽然普遍存在的过表达会导致蛹死亡，但组织特异性的dCAP-D3过表达会导致核质蛋白聚集体的形成，从而减缓有丝分裂前期的进展，这与dCAP-D3水平耗尽时观察到的结果相似。令人惊讶的是，dCAP-D3聚集体的形成导致了从中期到后期的更快转变。过表达的dCAP-D3蛋白不能在非分裂组织中沉淀其他凝缩素II亚基，但确实会引起基因表达的变化，这与在分裂组织和非分裂组织中dCAP-D3水平耗尽时所观察到的情况相反。我们的研究结果表明，改变dCAP-D3水平对有丝分裂时间、基因表达调控和生物体发育都有不利影响。综上所述，这些数据表明凝缩蛋白II在整个细胞周期中的不同作用可能是相互独立的，并且/或者dCAP-D3可能具有与其与凝缩蛋白II复合物相关的功能分离的功能。如果保守，这些发现可能对CAP-D3水平升高的肿瘤有影响。
The Condensin II complex plays important, conserved roles in genome organization throughout the cell cycle and in the regulation of gene expression. Previous studies have linked decreased Condensin II subunit expression with a variety of diseases. Here, we show that elevated levels of Condensin II subunits are detected in somatic cancers. To evaluate potential biological effects of elevated Condensin II levels, we overexpressed the Condensin II subunit, dCAP-D3 in Drosophila melanogaster larval tissues and examined the effects on the mitotic- and interphase-specific functions of Condensin II. Interestingly, while ubiquitous overexpression resulted in pupal lethality, tissue specific overexpression of dCAP-D3 caused formation of nucleoplasmic protein aggregates which slowed mitotic prophase progression, mimicking results observed when dCAP-D3 levels are depleted. Surprisingly, dCAP-D3 aggregate formation resulted in faster transitions from metaphase to anaphase. Overexpressed dCAP-D3 protein failed to precipitate other Condensin II subunits in nondividing tissues, but did cause changes to gene expression which occurred in a manner opposite of what was observed when dCAP-D3 levels were depleted in both dividing and nondividing tissues. Our findings show that altering dCAP-D3 levels in either direction has detrimental effects on mitotic timing, the regulation of gene expression, and organism development. Taken together, these data suggest that the different roles for Condensin II throughout the cell cycle may be independent of each other and/or that dCAP-D3 may possess functions that are separate from those involving its association with the Condensin II complex. If conserved, these findings could have implications for tumors harboring elevated CAP-D3 levels.