The Complex Containing Drosophila Myb and RB/E2F2 Regulates Cytokinesis in a Histone H2Av-Dependent Manner

The Complex Containing Drosophila Myb and RB/E2F2 Regulates Cytokinesis in a Histone H2Av-Dependent Manner
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DOI:
10.1128/mcb.01401-12
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发表时间:
2013-05-01
影响因子:
5.3
通讯作者:
Lipsick, Joseph S.
Lipsick, Joseph S.
中科院分区:
生物学2区
文献类型:
--
作者:
DeBruhl, Heather;Wen, Hong;Lipsick, Joseph S.

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在果蝇中,癌基因Myb的突变降低了有丝分裂基因如波罗和ial的表达,并引起多种有丝分裂缺陷,包括染色体凝聚和异常纺锤体的破坏。我们现在发现,双核细胞,胞质分裂失败的标志性表型,积累在Myb无效的卵泡细胞和翅盘上皮。Myb在通常抑制性的果蝇RBF、E2 F2和Myb(dREAM)/Myb-MuvB复合物中起激活剂的作用。dREAM亚基Mip 130或E2 F2的缺失抑制了Myb无效胞质分裂缺陷。因此,我们使用Myb无效双核细胞作为dREAM复合物转录抑制的定量表型读数。在不存在Myb的情况下,复合物对亚基E2 F2、Mip 120、Caf 1和Lin-52的剂量敏感,但对Mip 130或Mip 40不敏感。令人惊讶的是,His 2Av/H2A.z剂量的减少也抑制了Myb无效的双核细胞表型,表明这种变体组蛋白在dREAM复合物的转录抑制中的新作用。
In Drosophila, mutation of the oncogene Myb reduced the expression of mitotic genes, such as polo and ial, and caused multiple mitotic defects, including disrupted chromosome condensation and abnormal spindles. We now show that binucleate cells, the hallmark phenotype of cytokinesis failure, accumulate in Myb-null ovarian follicle cell and wing disc epithelia. Myb functions as an activator in the generally repressive Drosophila RBF, E2F2, and Myb (dREAM)/Myb-MuvB complex. Absence of the dREAM subunit Mip130 or E2F2 suppressed the Myb-null cytokinesis defect. Therefore, we used Myb-null binucleate cells as a quantitative phenotypic readout of transcriptional repression by the dREAM complex. In the absence of Myb, the complex was sensitive to the dose of the subunits E2F2, Mip120, Caf1, and Lin-52 but not Mip130 or Mip40. Surprisingly, reduction of the dose of His2Av/H2A.z also suppressed the Myb-null binucleate cell phenotype, suggesting a novel role for this variant histone in transcriptional repression by the dREAM complex.