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      Transcription Factor Binding Site Redundancy in Embryonic Enhancers of the Drosophila Bithorax Complex

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          Abstract

          The molecular control of gene expression in development is mediated through the activity of embryonic enhancer cis-regulatory modules. This activity is determined by the combination of repressor and activator transcription factors that bind at specific DNA sequences in the enhancer. A proposed mechanism to ensure a high fidelity of transcriptional output is functional redundancy between closely spaced binding sites within an enhancer. Here I show that at the bithorax complex in Drosophila there is selective redundancy for both repressor and activator factor binding sites in vivo. The absence of compensatory binding sites is responsible for two rare gain-of-function mutations in the complex.

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          Most cited references 31

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          The human genome browser at UCSC.

          As vertebrate genome sequences near completion and research refocuses to their analysis, the issue of effective genome annotation display becomes critical. A mature web tool for rapid and reliable display of any requested portion of the genome at any scale, together with several dozen aligned annotation tracks, is provided at http://genome.ucsc.edu. This browser displays assembly contigs and gaps, mRNA and expressed sequence tag alignments, multiple gene predictions, cross-species homologies, single nucleotide polymorphisms, sequence-tagged sites, radiation hybrid data, transposon repeats, and more as a stack of coregistered tracks. Text and sequence-based searches provide quick and precise access to any region of specific interest. Secondary links from individual features lead to sequence details and supplementary off-site databases. One-half of the annotation tracks are computed at the University of California, Santa Cruz from publicly available sequence data; collaborators worldwide provide the rest. Users can stably add their own custom tracks to the browser for educational or research purposes. The conceptual and technical framework of the browser, its underlying MYSQL database, and overall use are described. The web site currently serves over 50,000 pages per day to over 3000 different users.
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            The evolutionary significance of cis-regulatory mutations.

            For decades, evolutionary biologists have argued that changes in cis-regulatory sequences constitute an important part of the genetic basis for adaptation. Although originally based on first principles, this claim is now empirically well supported: numerous studies have identified cis-regulatory mutations with functionally significant consequences for morphology, physiology and behaviour. The focus has now shifted to considering whether cis-regulatory and coding mutations make qualitatively different contributions to phenotypic evolution. Cases in which parallel mutations have produced parallel trait modifications in particular suggest that some phenotypic changes are more likely to result from cis-regulatory mutations than from coding mutations.
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              A gene complex controlling segmentation in Drosophila.

               Edwin Lewis (1978)
              The bithorax gene complex in Drosophila contains a minimum of eight genes that seem to code for substances controlling levels of thoracic and abdominal development. The state of repression of at least four of these genes is controlled by cis-regulatory elements and a separate locus (Polycomb) seems to code for a repressor of the complex. The wild-type and mutant segmentation patterns are consistent with an antero-posterior gradient in repressor concentration along the embryo and a proximo-distal gradient along the chromosome in the affinities for repressor of each gene's cis-regulatory element.
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                Author and article information

                Affiliations
                Biology Department, Harvey Mudd College, Claremont, California 91711
                Author notes

                Supporting information is available online at http://www.g3journal.org/lookup/suppl/doi:10.1534/g3.111.001404/-/DC1

                [1 ]Address for correspondence: Robert A. Drewell, Biology Department, Harvey Mudd College, 301 Platt Boulevard, Claremont, CA 91711. E-mail: drewell@ 123456hmc.edu
                Contributors
                Role: Communicating editor
                Journal
                G3 (Bethesda)
                ggg
                ggg
                ggg
                G3: Genes|Genomes|Genetics
                Genetics Society of America
                2160-1836
                1 December 2011
                December 2011
                : 1
                : 7
                : 603-606
                3276168
                22384371
                GGG_001404
                10.1534/g3.111.001404
                (Communicating editor)
                Copyright © 2011 Drewell

                This is an open-access article distributed under the terms of the Creative Commons Attribution Unported License ( http://creativecommons.org/licenses/by/3.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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                Investigation
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                v1

                Genetics

                dna binding site, transcription factor, enhancer, cis-regulation, bithorax complex, drosophila

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