Transcriptome profiling of the C. elegans Rb ortholog reveals diverse developmental roles

Transcriptome profiling of the C. elegans Rb ortholog reveals diverse developmental roles
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DOI:
10.1016/j.ydbio.2007.02.021
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发表时间:
2007-05-15
影响因子:
2.7
通讯作者:
Fay, David S.
Fay, David S.
中科院分区:
生物学3区
文献类型:
--
作者:
Kirienko, Natalia V.;Fay, David S.

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LIN-35是哺乳动物口袋蛋白家族成员的单个线虫同源基因,pRb,第107页和第130页。为了深入了解Pocket蛋白在发育过程中的作用,对Lin-35突变体进行了微阵列分析。揭示了LIN-35的阶段特异性调控模式,表明LIN-35在不同的发育阶段发挥着不同的作用。LIN-35被发现抑制与幼虫细胞增殖有关的许多基因的表达,这一活动是与E2F一起进行的。此外,LIN-35被发现在胚胎发育过程中调节神经元基因,并在多个发育阶段调节肠道特异性GATA转录因子ELT-2的靶标。其他发现表明,LIN-35以一种独立于E2F的方式在胚胎细胞周期调节中发挥作用。LIN-35调控的基因与已知的苍蝇和哺乳动物口袋蛋白靶标的比较显示出高度重叠,表明口袋蛋白功能在不同的门中具有很强的保守性。基于微阵列结果和我们对线虫E2F共同序列的精炼,我们能够生成线虫中可能受E2F调控的基因的全面列表。这些结果表明,大量以前与细胞周期控制无关的基因在这一过程中具有潜在的作用。(C)2007 Elsevier Inc.保留所有权利。
LIN-35 is the single C. elegans ortholog of the mammalian pocket protein family members, pRb, p 107, and p 130. To gain insight into the roles of pocket proteins during development, a microarray analysis was performed with lin-35 mutants. Stage-specific regulation patterns were revealed, indicating that LIN-35 plays diverse roles at distinct developmental stages. LIN-35 was found to repress the expression of many genes involved in cell proliferation in larvae, an activity that is carried out in conjunction with E2F. In addition, LIN-35 was found to regulate neuronal genes during embryogenesis and targets of the intestinal-specific GATA transcription factor, ELT-2, at multiple developmental stages. Additional findings suggest that LIN-35 functions in cell cycle regulation in embryos in a manner that is independent of E2F. A comparison of LIN-35-regulated genes with known fly and mammalian pocket protein targets revealed a high degree of overlap, indicating strong conservation of pocket protein functions in diverse phyla. Based on microarray results and our refinement of the C. elegans E2F consensus sequence, we were able to generate a comprehensive list of putative E2F-regulated genes in C. elegans. These results implicate a large number of genes previously unconnected to cell cycle control as having potential roles in this process. (c) 2007 Elsevier Inc. All rights reserved.