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Distinct Roles of Broadly Expressed Repressors Support Dynamic Enhancer Action and Change in Time

Koromila, Theodora and Stathopoulos, Angelike (2019) Distinct Roles of Broadly Expressed Repressors Support Dynamic Enhancer Action and Change in Time. Cell Reports, 28 (4). pp. 855-863. ISSN 2211-1247. PMCID PMC6927530. https://resolver.caltech.edu/CaltechAUTHORS:20190723-101525324

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Abstract

How broadly expressed repressors regulate gene expression is incompletely understood. To gain insight, we investigated how Suppressor of Hairless—Su(H)—and Runt regulate expression of bone morphogenetic protein (BMP) antagonist short-gastrulation via the sog_Distal enhancer. A live imaging protocol was optimized to capture this enhancer’s spatiotemporal output throughout the early Drosophila embryo, finding in this context that Runt regulates transcription initiation, Su(H) regulates transcription rate, and both factors control spatial expression. Furthermore, whereas Su(H) functions as a dedicated repressor, Runt temporally switches from repressor to activator. Our results demonstrate that broad repressors play temporally distinct roles and contribute to dynamic gene expression. Both Run and Su(H)’s ability to influence the spatiotemporal domains of gene expression may serve to counterbalance activators and function in this manner as important regulators of the maternal-to-zygotic transition in early embryos.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1016/j.celrep.2019.06.063DOIArticle
http://www.ncbi.nlm.nih.gov/pmc/articles/pmc6927530/PubMed CentralArticle
ORCID:
AuthorORCID
Koromila, Theodora0000-0001-5504-1369
Stathopoulos, Angelike0000-0001-6597-2036
Additional Information:© 2019 The Authors. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). Received 30 October 2018, Revised 2 May 2019, Accepted 17 June 2019, Available online 23 July 2019. We are grateful to Sofia Sakellaridi and Boris Gutman for computational analysis support; Nathalie Dostatni, Hernan Garcia, and Mike Levine for providing plasmids and fly stocks; Justin Bois, Frank Macabenta, Susie Newcomb, and James McGehee for comments on the manuscript; and Peter Gergen and Andres Collazo for helpful discussions. This study was supported by NIH grant R35GM118146 to A.S. Author Contributions: A.S. and T.K conceived the project and planned the experimental approach. A.S. directed the project. T.K. performed the experiments. T.K. designed the image analysis pipeline, wrote the scripts, and carried out the quantitative analyses. A.S. and T.K. analyzed the data. A.S. and T.K. wrote the manuscript. The authors declare no competing interests.
Funders:
Funding AgencyGrant Number
NIHR35GM118146
Subject Keywords:Drosophila melanogaster; short gastrulation; sog; Runt; Run; Suppressor of Hairless; Su(H); cis-regulatory mechanism; enhancer; dual-function transcription factor; maternal-to-zygotic transition
Issue or Number:4
PubMed Central ID:PMC6927530
Record Number:CaltechAUTHORS:20190723-101525324
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20190723-101525324
Official Citation:Theodora Koromila, Angelike Stathopoulos, Distinct Roles of Broadly Expressed Repressors Support Dynamic Enhancer Action and Change in Time, Cell Reports, Volume 28, Issue 4, 2019, Pages 855-863.e5, ISSN 2211-1247, https://doi.org/10.1016/j.celrep.2019.06.063. (http://www.sciencedirect.com/science/article/pii/S2211124719308368)
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:97351
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:23 Jul 2019 20:43
Last Modified:03 Apr 2020 23:28

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