Hunchback is counter-repressed to regulate even-skipped stripe 2 expression in Drosophila embryos

Vincent, Ben J.; Staller, Max V.; López-Rivera, Francheska; Bragdon, Meghan D. J.; Pym, Edward C.G.; Biette, Kelly M.; Wunderlich, Zeba; Harden, Timothy T.; Estrada, Javier; DePace, Angela H.

doi:10.1371/journal.pgen.1007644

Cited by 27 publications

(21 citation statements)

References 73 publications

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“…Additional work will be necessary to determine whether this correlation between rising Hunchback levels and increased stripe activity can be reconciled with the counter-repression hypothesis proposed in ref. 80. Finally, we note that the striking absence of a direct functional role for Bicoid in the regulation of either phenomenon suggests that, while Bicoid is almost certainly necessary for the expression of eve stripe 2 (16), it does not play a direct role in dictating the magnitude or duration of eve stripe 2 transcription.…”

Section: Discussionmentioning

confidence: 84%

Multimodal transcriptional control of pattern formation in embryonic development

Lammers

Galstyan

Reimer

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

101

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Predicting how interactions between transcription factors and regulatory DNA sequence dictate rates of transcription and, ultimately, drive developmental outcomes remains an open challenge in physical biology. Using stripe 2 of the even-skipped gene in Drosophila embryos as a case study, we dissect the regulatory forces underpinning a key step along the developmental decision-making cascade: the generation of cytoplasmic mRNA patterns via the control of transcription in individual cells. Using live imaging and computational approaches, we found that the transcriptional burst frequency is modulated across the stripe to control the mRNA production rate. However, we discovered that bursting alone cannot quantitatively recapitulate the formation of the stripe and that control of the window of time over which each nucleus transcribes even-skipped plays a critical role in stripe formation. Theoretical modeling revealed that these regulatory strategies (bursting and the time window) respond in different ways to input transcription factor concentrations, suggesting that the stripe is shaped by the interplay of 2 distinct underlying molecular processes.

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Section: Discussionmentioning

confidence: 84%

Multimodal transcriptional control of pattern formation in embryonic development

Lammers

Galstyan

Reimer

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

101

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“…Rather, we suggest that Hb may be preventing activation by Cad, despite its presence. Hb and Cad play antagonistic roles at the enhancers of other genes, such as even skipped (Clyde et al, 2003;Small et al, 1992;Vincent et al, 2018). Therefore, co-occupancy of the gt_(-3) enhancer by Hb and Cad is not unprecedented, but the mechanism by which Hb prevents gt activation is unclear.…”

Section: Discussionmentioning

confidence: 99%

De novo recruitment of Polycomb-group proteins in Drosophila embryos

Abed

Ghotbi

et al. 2018

Development

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Polycomb-group (PcG)-mediated transcriptional repression of target genes can be delineated into two phases. First, following initial repression of target genes by gene-specific transcription factors, PcG proteins recognize the repressed state and assume control of the genes' repression. Second, once the silenced state is established, PcG proteins may maintain repression through an indefinite number of cell cycles. Little is understood about how PcG proteins initially recognize the repressed state of target genes and the steps leading to de novo establishment of PcG-mediated repression. We describe a genetic system in which a Drosophila PcG target gene, giant (gt), is ubiquitously repressed during early embryogenesis by a maternally expressed transcription factor, and show the temporal recruitment of components of three PcG protein complexes: PhoRC, PRC1 and PRC2. We show that de novo PcG recruitment follows a temporal hierarchy in which PhoRC stably localizes at the target gene at least 1 h before stable recruitment of PRC2 and concurrent trimethylation of histone H3 at lysine 27 (H3K27me3). The presence of PRC2 and increased levels of H3K27me3 are found to precede stable binding by PRC1.

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“…Interestingly, deletion of Runt's C-terminal 25 amino acids, including the VWRPY motif, prevents Runt from activating slp1; however amino acids other that the VWRPY motif appear to be involved as Gro appears to play no role in regulating the DESE enhancer. Here we provide evidence that Runt activates SxlPe by interfering with Groucho mediated repression suggesting that Runt's role at SxlPe is as a counter-repressor (PINTO et al 2015;VINCENT et al 2018). First, we showed that deletion of just the Gro-interacting WRPY sequence rendered a runt transgene that normally provides full XSE function, unable to activate SxlPe (Fig.…”

Section: )mentioning

confidence: 65%

“…We found that deletion of the WRPY sequence eliminated Runt's ability to activate SxlPe, but that Runt's transcriptional activation function was restored when the higher-affinity WRPW sequence was used. Since Runt's ability to activate SxlPe depends both on the presence of a functional corepressor-interacting motif, and an intact DNA binding domain, the simplest interpretation is that Runt activates SxlPe by acting as a "counter-repressor" of Gro function (PINTO et al 2015;VINCENT et al 2018). We also demonstrate that Runt is needed only after the onset of Sxl…”

Section: Introductionmentioning

confidence: 64%

Evidence that Runt Acts as a Counter-Repressor of Groucho duringDrosophila melanogasterPrimary Sex Determination

Erickson

Mahadevaraju

2019

Preprint

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Runx proteins are bifunctional transcription factors that both repress and activate transcription in animal cells. Typically Runx proteins work in concert with other transcriptional regulators, including coactivators and co-repressors to mediate their biological effects. In Drosophila melanogaster the archetypal Runx protein, Runt, functions in numerous processes including segmentation, neurogenesis and sex determination. During primary sex determination Runt acts as one of four X-linked signal element (XSE) proteins that direct female-specific activation of the establishmen promoter (Pe) of the master regulatory gene Sex-lethal (Sxl). Successful activation of SxlPe requires that the XSE proteins overcome the repressive effects of maternally deposited Groucho (Gro), a potent co-repressor of the Gro/TLE family. Runx proteins, including Runt, contain a C-terminal peptide, VWRPY, known to bindto Gro/TLE proteins to mediate transcriptional repression. We show that Runt's VWRPY co-repressorinteraction domain is needed for Runt to activate SxlPe. Deletion of the Gro-interaction domain eliminates Runt-ability to activate SxlPe, whereas replacement with a higher affinity, VWRPW, sequence promotes Runt-mediated transcription. This suggest that Runt activates SxlPe by antagonizing Gro function, a conclusion consist with earlier findings that Runt is needed for Sxl expression only in embryonic regions with high Gro activity. Surprisingly we found that Runt is not required for the initial activation activation of SxlPe. Instead, Runt is needed to keep SxlPe active during the subsequent period of high-level Sxl transcription suggesting that Runt helps amplfy the difference between female and male XSE signals by counterrepressing Gro in female, but not in male, embryos.

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Hunchback is counter-repressed to regulate even-skipped stripe 2 expression in Drosophila embryos

Cited by 27 publications

References 73 publications

Multimodal transcriptional control of pattern formation in embryonic development

Multimodal transcriptional control of pattern formation in embryonic development

De novo recruitment of Polycomb-group proteins in Drosophila embryos

Evidence that Runt Acts as a Counter-Repressor of Groucho duringDrosophila melanogasterPrimary Sex Determination

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