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Autoregulatory Feedback Controls Sequential Action of cis-Regulatory Modules at the brinker Locus

Dunipace, Leslie and Saunders, Abbie and Ashe, Hilary L. and Stathopoulos, Angelike (2013) Autoregulatory Feedback Controls Sequential Action of cis-Regulatory Modules at the brinker Locus. Developmental Cell, 26 (5). pp. 536-543. ISSN 1534-5807. PMCID PMC3782659. doi:10.1016/j.devcel.2013.08.010.

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cis-regulatory modules (CRMs) act sequentially to regulate temporal expression of genes, but how the switch from one to the next is accomplished is not well understood. To provide insight, here we investigate the cis-regulatory system controlling brinker (brk) expression in the Drosophila embryo. Two distally located CRMs support expression at different times, while a promoter-proximal element (PPE) is required to support their action. In the absence of Brk protein itself or upon mutagenesis of Brk binding sites within the PPE, the late-acting CRM, specifically, is delayed. This block to late-acting CRM function appears to be removed when the early-acting CRM is also deleted. These results demonstrate that autoregulatory feedback is necessary for the early-acting CRM to disengage from the promoter so that the late-acting CRM may act. Autoregulation may be a commonly used mechanism to control sequential CRM action necessary for dynamic gene expression throughout the course of development.

Item Type:Article
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URLURL TypeDescription CentralArticle
Dunipace, Leslie0000-0002-1739-6537
Stathopoulos, Angelike0000-0001-6597-2036
Additional Information:© 2013 The Authors. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Open access under CC BY license. Received: January 18, 2013. Revised: July 17, 2013. Accepted: August 14, 2013. Published: September 16, 2013. We thank members of the Stathopoulos laboratory for helpful discussions. In particular, we are grateful to A. Ozdemir for initial testing of Twist ChIP-seq peaks at the brk locus and to V. Stepanik for comments on the manuscript. This study was supported by NIH grant R01GM077668 to A.S. and Wellcome Trust grant 092005/Z/10/Z to H.L.A.
Funding AgencyGrant Number
Wellcome Trust092005/Z/10/Z
Issue or Number:5
PubMed Central ID:PMC3782659
Record Number:CaltechAUTHORS:20131121-114801430
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Official Citation:Leslie Dunipace, Abbie Saunders, Hilary L. Ashe, Angelike Stathopoulos, Autoregulatory Feedback Controls Sequential Action of cis-Regulatory Modules at the brinker Locus, Developmental Cell, Volume 26, Issue 5, 16 September 2013, Pages 536-543, ISSN 1534-5807, (
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:42616
Deposited By: Ruth Sustaita
Deposited On:21 Nov 2013 21:27
Last Modified:10 Nov 2021 16:25

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