Transcription Factor Networks in Drosophila melanogaster

Rhee, David Y.; Cho, Dong-Yeon; Zhai, Bo; Slattery, Matthew; Ma, Lijia; Mintseris, Julian; Wong, Christina S.F.; White, Kevin P.; Celniker, S; Przytycka, Teresa M.; Gygi, Steven P.; Obar, Robert A.; Artavanis‐Tsakonas, Spyros

doi:10.1016/j.celrep.2014.08.038

Cited by 88 publications

(78 citation statements)

References 77 publications

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“…Our GO term analysis on the 100 genes with the strongest association with g max of G 50 8750 illuminated an appreciable number of terms linked to regulatory functions, including mRNA processing (Le Hir et al 2003), transcription initiation (Shilatifard et al 2003), and transcription factors that underlie gene regulatory networks (Erwin and Davidson 2009). A recent study constructing transcription factor protein interaction networks in Drosophila has indicated that many hundreds of transcription factor proteins display bivariate interactions, with up to 63% of 647 known or putative transcription factors forming a single protein interaction net-work (Rhee et al 2014). The genetic variance captured by g max represents the possible genetic control of such widespread protein networks.…”

Section: The Extent Of Genetic Covariance Among Gene Expression Traitsmentioning

confidence: 99%

The Phenome-Wide Distribution of Genetic Variance

Blows¹,

Allen²,

Chenoweth³

et al. 2015

The American Naturalist

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JSTOR is a not-for-profit service that helps scholars, researchers, and students discover, use, and build upon a wide range of content in a trusted digital archive. We use information technology and tools to increase productivity and facilitate new forms of scholarship. For more information about JSTOR, please contact support@jstor.org. abstract: A general observation emerging from estimates of additive genetic variance in sets of functionally or developmentally related traits is that much of the genetic variance is restricted to few trait combinations as a consequence of genetic covariance among traits. While this biased distribution of genetic variance among functionally related traits is now well documented, how it translates to the broader phenome and therefore any trait combination under selection in a given environment is unknown. We show that 8,750 gene expression traits measured in adult male Drosophila serrata exhibit widespread genetic covariance among random sets of five traits, implying that pleiotropy is common. Ultimately, to understand the phenome-wide distribution of genetic variance, very large additive genetic variancecovariance matrices (G) are required to be estimated. We draw upon recent advances in matrix theory for completing high-dimensional matrices to estimate the 8,750-trait G and show that large numbers of gene expression traits genetically covary as a consequence of a single genetic factor. Using gene ontology term enrichment analysis, we show that the major axis of genetic variance among expression traits successfully identified genetic covariance among genes involved in multiple modes of transcriptional regulation. Our approach provides a practical empirical framework for the genetic analysis of highdimensional phenome-wide trait sets and for the investigation of the extent of high-dimensional genetic constraint.

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Section: The Extent Of Genetic Covariance Among Gene Expression Traitsmentioning

confidence: 99%

The Phenome-Wide Distribution of Genetic Variance

Blows¹,

Allen²,

Chenoweth³

et al. 2015

The American Naturalist

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“…As Nerfin-1 is a possible interacting partner of the Hippo effectors Scalloped and Yorkie (Feng et al, 2013;Rhee et al, 2014), we sought to determine whether Nerfin-1 functions in the optic lobe. Throughout the analysis, two cross-sections of optic lobe were analyzed (Fig.…”

Section: Nerfin-1 Is Expressed Mainly In Early-stage Medulla Neuronsmentioning

confidence: 99%

Prevention of medulla neuron dedifferentiation by Nerfin-1 requires inhibition of Notch activity

Xue

Yin

et al. 2017

Development

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The Drosophila larval central nervous system comprises the central brain, ventral nerve cord and optic lobe. In these regions, neuroblasts (NBs) divide asymmetrically to self-renew and generate differentiated neurons or glia. To date, mechanisms of preventing neuron dedifferentiation are still unclear, especially in the optic lobe. Here, we show that the zinc-finger transcription factor Nerfin-1 is expressed in early-stage medulla neurons and is essential for maintaining their differentiation. Loss of Nerfin-1 activates Notch signaling, which promotes neuron-to-NB reversion. Repressing Notch signaling largely rescues dedifferentiation in nerfin-1 mutant clones. Thus, we conclude that Nerfin-1 represses Notch activity in medulla neurons and prevents them from dedifferentiation.

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“…2-5). The physical interaction between Enok and Elg1 complexes is also supported by a recent large-scale study on protein-protein interactions (Rhee et al 2014). This study reported the interacting partners of 459 Drosophila transcription-related factors, and four subunits of the Elg1 complex (Elg1, Rfc4, Rfc38, and Rfc3) were identified by affinity purification using Br140 as the bait.…”

Section: Discussionmentioning

confidence: 55%

The Enok acetyltransferase complex interacts with Elg1 and negatively regulates PCNA unloading to promote the G1/S transition

et al. 2016

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KAT6 histone acetyltransferases (HATs) are highly conserved in eukaryotes and are involved in cell cycle regulation. However, information regarding their roles in regulating cell cycle progression is limited. Here, we report the identification of subunits of the Drosophila Enok complex and demonstrate that all subunits are important for its HAT activity. We further report a novel interaction between the Enok complex and the Elg1 proliferating cell nuclear antigen (PCNA)-unloader complex. Depletion of Enok in S2 cells resulted in a G1/S cell cycle block, and this block can be partially relieved by depleting Elg1. Furthermore, depletion of Enok reduced the chromatin-bound levels of PCNA in both S2 cells and early embryos, suggesting that the Enok complex may interact with the Elg1 complex and downregulate its PCNA-unloading function to promote the G1/S transition. Supporting this hypothesis, depletion of Enok also partially rescued the endoreplication defects in Elg1-depleted nurse cells. Taken together, our study provides novel insights into the roles of KAT6 HATs in cell cycle regulation through modulating PCNA levels on chromatin.

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Transcription Factor Networks in Drosophila melanogaster

Cited by 88 publications

References 77 publications

The Phenome-Wide Distribution of Genetic Variance

The Phenome-Wide Distribution of Genetic Variance

Prevention of medulla neuron dedifferentiation by Nerfin-1 requires inhibition of Notch activity

The Enok acetyltransferase complex interacts with Elg1 and negatively regulates PCNA unloading to promote the G1/S transition

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