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Complex interactions between cis-regulatory modules in native conformation are critical for Drosophila snail expression

Dunipace, Leslie and Ozdemir, Anil and Stathopoulos, Angelike (2011) Complex interactions between cis-regulatory modules in native conformation are critical for Drosophila snail expression. Development, 138 (18). pp. 4075-4084. ISSN 0950-1991. PMCID PMC3160101.

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It has been shown in several organisms that multiple cis-regulatory modules (CRMs) of a gene locus can be active concurrently to support similar spatiotemporal expression. To understand the functional importance of such seemingly redundant CRMs, we examined two CRMs from the Drosophila snail gene locus, which are both active in the ventral region of pre-gastrulation embryos. By performing a deletion series in a ~25 kb DNA rescue construct using BAC recombineering and site-directed transgenesis, we demonstrate that the two CRMs are not redundant. The distal CRM is absolutely required for viability, whereas the proximal CRM is required only under extreme conditions such as high temperature. Consistent with their distinct requirements, the CRMs support distinct expression patterns: the proximal CRM exhibits an expanded expression domain relative to endogenous snail, whereas the distal CRM exhibits almost complete overlap with snail except at the anterior-most pole. We further show that the distal CRM normally limits the increased expression domain of the proximal CRM and that the proximal CRM serves as a 'damper' for the expression levels driven by the distal CRM. Thus, the two CRMs interact in cis in a non-additive fashion and these interactions may be important for fine-tuning the domains and levels of gene expression.

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Stathopoulos, Angelike0000-0001-6597-2036
Additional Information:© 2011 Published by The Company of Biologists Ltd. Accepted 15 July 2011. We are grateful to Eric Davidson (Caltech) and to the Stathopoulos lab for helpful discussions. In addition, we thank Sagar Damle (Caltech) for advice on BAC recombineering. This work was funded through NIGMS R01 grant GM077668 (A.S.) and corresponding ARRA supplement from the NIH. Deposited in PMC for release after 12 months.
Funding AgencyGrant Number
Subject Keywords:Cis-regulatory modules; Gene expression; Drosophila melanogaster; snail; Developmental patterning; Repression; Huckebein
Issue or Number:18
PubMed Central ID:PMC3160101
Record Number:CaltechAUTHORS:20110912-092711852
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:25291
Deposited By: Tony Diaz
Deposited On:12 Sep 2011 17:05
Last Modified:03 Oct 2019 03:04

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