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High levels of Dorsal transcription factor downregulate, not promote, snail expression by regulating enhancer action

Irizarry, Jihyun and McGehee, James and Stathopoulos, Angelike (2021) High levels of Dorsal transcription factor downregulate, not promote, snail expression by regulating enhancer action. . (Unpublished)

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In Drosophila embryos, genes expressed along the dorsal-ventral axis are responsive to concentration of the Dorsal (Dl) transcription factor, which varies in space; however, levels of this morphogen also build over time. Since expression of high-threshold Dl target genes such as snail (sna) is supported before Dl levels peak, it is unclear what role increasing levels have if any. Here we investigated action of two enhancers that control sna expression in embryos, demonstrating using genome editing that Dl binding sites within one enhancer located promoter proximally, sna.prox, can limit the ability of the other distally-located enhancer, sna.dis, to increase sna levels. In addition, MS2-MCP live imaging was used to study sna transcription rate in wildtype, dl heterozygote, and a background in which a photo-sensitive degron is fused to Dl (dl-BLID). The results demonstrate that, when Dl levels are high, Dl acts through sna.prox to limit the activity of sna.dis and thereby influence sna transcription rate. In contrast, when Dl levels are kept low using dl-BLID, sna.prox positively influences sna transcription rate. Collectively, our data support the view that Dl’s effect on gene expression changes over time, switching from promoting sna expression at low concentration to dampening sna expression at high concentration by regulating enhancer interactions. We propose this differential action of the Dl morphogen is likely supported by occupancy of this factor first to high and then low affinity binding sites over time as Dl levels rise to coordinate action of these two co-acting enhancers.

Item Type:Report or Paper (Discussion Paper)
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URLURL TypeDescription Paper
Irizarry, Jihyun0000-0003-3967-2288
McGehee, James0000-0002-9353-1235
Stathopoulos, Angelike0000-0001-6597-2036
Additional Information:The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC 4.0 International license. This version posted January 11, 2021. We are grateful to Mike Levine for providing the sna. MS2, and MCP.GFP fly stocks, Hernan Garcia for providing the MCP.mCherry fly stocks and Leslie Dunipace for comments on the manuscript. This study was supported by funding from National Institutes of Health grant R35GM118146 to A.S. Author Contributions: A.S. and J.I. conceived the project and planned the experimental approach. A.S. directed the project. J.I. performed all experiments, and J.M. performed all quantitative analysis of imaging data. Data were analyzed by J.I., J.M., and A.S. The manuscript was written by J.I. and A.S. with edits provided by J.M. The authors declare no competing interests.
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Subject Keywords:Drosophila melanogaster , snail , Dorsal, morphogen, cis-regulatory mechanisms, shadow enhancer, photosensitive degron B-LID
Record Number:CaltechAUTHORS:20210115-071336776
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Official Citation:High levels of Dorsal transcription factor downregulate, not promote, snail expression by regulating enhancer action. Jihyun Irizarry, James McGehee, Angelike Stathopoulos. bioRxiv 2021.01.11.426256; doi:
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:107504
Deposited By: Tony Diaz
Deposited On:15 Jan 2021 16:45
Last Modified:16 Nov 2021 19:03

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