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

DeBruhl, Heather; Wen, Hong; Lipsick, Joseph S.

doi:10.1128/mcb.01401-12

Cited by 22 publications

(23 citation statements)

References 72 publications

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“…In Drosophila, reduction of function of H2A.Z or four different DREAM components similarly suppressed a cytokinesis defect (DeBruhl et al 2013). A Drosophila E2F target gene reporter is also derepressed by loss of components of the Swr1 complex, which is involved in H2A.Z deposition (Lu et al 2007).…”

Section: Discussionmentioning

confidence: 99%

The DREAM complex promotes gene body H2A.Z for target repression

et al. 2015

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The DREAM (DP, Retinoblastoma [Rb]-like, E2F, and MuvB) complex controls cellular quiescence by repressing cell cycle genes, but its mechanism of action is poorly understood. Here we show that Caenorhabditis elegans DREAM targets have an unusual pattern of high gene body HTZ-1/H2A.Z. In mutants of lin-35, the sole p130/Rb-like gene in C. elegans, DREAM targets have reduced gene body HTZ-1/H2A.Z and increased expression. Consistent with a repressive role for gene body H2A.Z, many DREAM targets are up-regulated in htz-1/ H2A.Z mutants. Our results indicate that the DREAM complex facilitates high gene body HTZ-1/H2A.Z, which plays a role in target gene repression.

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Section: Discussionmentioning

confidence: 99%

The DREAM complex promotes gene body H2A.Z for target repression

et al. 2015

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“…Several studies suggest roles for NuA4 and H2Av in regulation of E2F target genes and genetic interactions with DREAM/MMB components (Ceol and Horvitz 2004;Lu et al 2007;DeBruhl et al 2013;Latorre et al 2015). Mammalian studies implicate Tip60/NuA4 as a transcriptional activator of E2F target genes, whereas a subset of NuA4 components in Drosophila cell culture were shown to repress E2F transcriptional targets (Lu et al 2007).…”

Section: The Nua4 Complexmentioning

confidence: 99%

“…However, the NuA4 complex also acts as an essential repressor of gene expression in certain contexts, such as embryonic stem cells (Fazzio et al 2008;Chen et al 2013), and can promote closed chromatin formation in flies (Qi et al 2006). Furthermore, NuA4 components paradoxically act as both tumor suppressors and oncogenes, leaving their positive vs. negative roles in cell cycle control unresolved (Sapountzi et al 2006;Judes et al 2015).Several studies suggest roles for NuA4 and H2Av in regulation of E2F target genes and genetic interactions with DREAM/MMB components (Ceol and Horvitz 2004;Lu et al 2007;DeBruhl et al 2013;Latorre et al 2015). Mammalian studies implicate Tip60/NuA4 as a transcriptional activator of E2F target genes, whereas a subset of NuA4 components in Drosophila cell culture were shown to repress E2F transcriptional targets (Lu et al 2007).…”

mentioning

confidence: 99%

Roles for the Histone Modifying and Exchange Complex NuA4 in Cell Cycle Progression in Drosophila melanogaster

Flegel¹,

Grushko²,

Bolin³

et al. 2016

Genetics

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Robust and synchronous repression of E2F-dependent gene expression is critical to the proper timing of cell cycle exit when cells transition to a postmitotic state. Previously NuA4 was suggested to act as a barrier to proliferation in Drosophila by repressing E2F-dependent gene expression. Here we show that NuA4 activity is required for proper cell cycle exit and the repression of cell cycle genes during the transition to a postmitotic state in vivo. However, the delay of cell cycle exit caused by compromising NuA4 is not due to additional proliferation or effects on E2F activity. Instead NuA4 inhibition results in slowed cell cycle progression through late S and G2 phases due to aberrant activation of an intrinsic p53-independent DNA damage response. A reduction in NuA4 function ultimately produces a paradoxical cell cycle gene expression program, where certain cell cycle genes become derepressed in cells that are delayed during the G2 phase of the final cell cycle. Bypassing the G2 delay when NuA4 is inhibited leads to abnormal mitoses and results in severe tissue defects. NuA4 physically and genetically interacts with components of the E2F complex termed Drosophila, Rbf, E2F and Myb/Multi-vulva class B (DREAM/MMB), and modulates a DREAM/MMB-dependent ectopic neuron phenotype in the posterior wing margin. However, this effect is also likely due to the cell cycle delay, as simply reducing Cdk1 is sufficient to generate a similar phenotype. Our work reveals that the major requirement for NuA4 in the cell cycle in vivo is to suppress an endogenous DNA damage response, which is required to coordinate proper S and G2 cell cycle progression with differentiation and cell cycle gene expression.KEYWORDS DNA damage; proliferation; H2Av; cell cycle checkpoint; cell cycle exit A conserved eukaryotic transcriptional oscillator controls cell cycle gene expression in proliferating cells and underlies the well-studied Cyclin/Cdk cell cycle protein oscillator (Orlando et al. 2008;Oikonomou and Cross 2010). In metazoans, this oscillator depends upon transcriptional activation of several hundred cell cycle genes, initiated by E2F transcription factor complexes followed by E2F inhibition (or degradation) (Shibutani et al. 2008;Zielke et al. 2011;Sadasivam and Decaprio 2013). This generates an oscillation of chromatin opening and closing at cell cycle genes that is thought to properly coordinate G1/S and G2/M gene expression as well as the transition to a noncycling state (Litovchick et al. 2007(Litovchick et al. , 2011Forristal et al. 2014). Disruption of this coordination can affect cell cycle progression by causing inappropriate gene expression (Reis and Edgar 2004;Wen et al. 2008;Forristal et al. 2014). While the oscillation of E2F activity is required for robust cell cycle gene expression Korenjak et al. 2012), E2F complexes are not absolutely essential for cell cycle progression or timely cell cycle exit in Drosophila (Frolov et al. 2001(Frolov et al. , 2005. In the absence of E2F activity there must be E2F-independ...

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“…The dREAM/MMB complex is evolutionarily conserved; human has an equivalent complex called DREAM/LINC complex (Schmit et al 2007). A growing body of evidence supports the idea that the dREAM/MMB complex has distinct functions and components in different cellular contexts (Georlette et al 2007;Debruhl et al 2013). Using a dsRNA-based knockdown system, the modifier screening for E2F transcriptional activity has been done, and identified l(3)malignant brain tumor (l(3)mbt) (Lu et al 2007).…”

Section: Regulatory Machinery Of Rb/e2f/dp Pathwaymentioning

confidence: 99%

Regulatory system for the G1‐arrest during neuronal development in Drosophila

Tsuda

Lim

2014

Dev Growth Differ

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Neuronal network consists of many types of neuron and glial cells. This diversity is guaranteed by the constant cell proliferation of neuronal stem cells following stop cell cycle re-entry, which leads to differentiation during development. Neuronal differentiation occurs mainly at the specific cell cycle phase, the G1 phase. Therefore, cell cycle exit at the G1 phase is quite an important issue in understanding the process of neuronal cell development. Recent studies have revealed that aberrant S phase re-entry from the G1 phase often links cellular survival. In this review we discuss the different types of G1 arrest on the process of neuronal development in Drosophila. We also describe the issue that aberrant S phase entry often causes apoptosis, and the same mechanism might contribute to sensory organ defects, such as deafness.

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

Cited by 22 publications

References 72 publications

The DREAM complex promotes gene body H2A.Z for target repression

The DREAM complex promotes gene body H2A.Z for target repression

Roles for the Histone Modifying and Exchange Complex NuA4 in Cell Cycle Progression in Drosophila melanogaster

Regulatory system for the G1‐arrest during neuronal development in Drosophila

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