A simple principle concerning the robustness of protein complex activity to changes in gene expression-3

<p><b>Copyright information:</b></p><p>Taken from "A simple principle concerning the robustness of protein complex activity to changes in gene expression"</p><p>http://www.biomedcentral.com/1752-0509/2/1</p><p>BMC Systems Biology 2008;2():1-1.</p><p>Published online 2 Jan 2008</p><p>PMCID:PMC2242779.</p><p></p>iched amongst the subunits of protein complexes. In contrast genes with over-expression phenotypes are equally represented amongst protein complex subunits and other genes. The graph shows the percentage of genes found in MIPS protein complexes and the percentage of all other genes that have each phenotype. ** Chi square test p < 0.05 for difference between protein complex subunits and all genes

A simple principle concerning the robustness of protein complex activity to changes in gene expression-1

<p><b>Copyright information:</b></p><p>Taken from "A simple principle concerning the robustness of protein complex activity to changes in gene expression"</p><p>http://www.biomedcentral.com/1752-0509/2/1</p><p>BMC Systems Biology 2008;2():1-1.</p><p>Published online 2 Jan 2008</p><p>PMCID:PMC2242779.</p><p></p>st to an increase, but not to a decrease in the expression levels of individual subunits

A simple principle concerning the robustness of protein complex activity to changes in gene expression-0

<p><b>Copyright information:</b></p><p>Taken from "A simple principle concerning the robustness of protein complex activity to changes in gene expression"</p><p>http://www.biomedcentral.com/1752-0509/2/1</p><p>BMC Systems Biology 2008;2():1-1.</p><p>Published online 2 Jan 2008</p><p>PMCID:PMC2242779.</p><p></p>st to an increase, but not to a decrease in the expression levels of individual subunits

A simple principle concerning the robustness of protein complex activity to changes in gene expression-2

<p><b>Copyright information:</b></p><p>Taken from "A simple principle concerning the robustness of protein complex activity to changes in gene expression"</p><p>http://www.biomedcentral.com/1752-0509/2/1</p><p>BMC Systems Biology 2008;2():1-1.</p><p>Published online 2 Jan 2008</p><p>PMCID:PMC2242779.</p><p></p>uctural components of protein complexes as defined by Gavin (2006). The percentages of all genes are shown for comparison. Inset: schematic representation of the overlap between the datasets used. Only 21 genes are found exclusively in modules, so we did not test these as a separate category. ** Fisher's exact test p < 0.0001 for difference between genes with the particular phenotype and all genes without that phenotype

Parallel Evolution of Chordate <i>Cis-</i>Regulatory Code for Development

<div><p>Urochordates are the closest relatives of vertebrates and at the larval stage, possess a characteristic bilateral chordate body plan. In vertebrates, the genes that orchestrate embryonic patterning are in part regulated by highly conserved non-coding elements (CNEs), yet these elements have not been identified in urochordate genomes. Consequently the evolution of the <i>cis-</i>regulatory code for urochordate development remains largely uncharacterised. Here, we use genome-wide comparisons between <i>C. intestinalis</i> and <i>C. savignyi</i> to identify putative urochordate <i>cis-</i>regulatory sequences. <i>Ciona</i> conserved non-coding elements (ciCNEs) are associated with largely the same key regulatory genes as vertebrate CNEs. Furthermore, some of the tested ciCNEs are able to activate reporter gene expression in both zebrafish and <i>Ciona</i> embryos, in a pattern that at least partially overlaps that of the gene they associate with, despite the absence of sequence identity. We also show that the ability of a ciCNE to up-regulate gene expression in vertebrate embryos can in some cases be localised to short sub-sequences, suggesting that functional cross-talk may be defined by small regions of ancestral regulatory logic, although functional sub-sequences may also be dispersed across the whole element. We conclude that the structure and organisation of <i>cis-</i>regulatory modules is very different between vertebrates and urochordates, reflecting their separate evolutionary histories. However, functional cross-talk still exists because the same repertoire of transcription factors has likely guided their parallel evolution, exploiting similar sets of binding sites but in different combinations.</p></div

Relative positions of CNEs in <i>Ciona</i> and vertebrate Meis genes.

<p>Pink boxes denote coding exons showing similar gene structures in all 3 genes (<i>Ciona</i> lacks the twelfth exon). Blue arrowheads denote CNE positions (with numbers above if more than 1). Green arrows indicate the most distal upstream and downstream distances of CNEs from the coding sequence in each case. Not to scale.</p

Functional analysis of Pax6_ciCNE2 deletion constructs.

<p>(A) Schematic representation and quantification of the constructs injected in the zebrafish embryos to examine their enhancer activity. The numbers in parentheses indicate the length of each construct. (B) View of a 48 hpf embryo injected with the full length CNE2 expressing GFP in sensory neurons (arrow). In the embryos injected with DCNE2-1 (C) or DCNE2-2 (D) GFP is detected in sensory neurons (arrow). The minimal construct DCNE2-1-2+DCNE2-2-1 (E) is able to drive GFP expression in neurons along the spinal cord (arrow).</p

Analysis of ciCNEs in <i>C. intestinalis</i> embryos.

<p>(A) Dorsal view of the head of a tailbud embryo electroporated with Pax6_ciCNE2. Reporter expression (arrow, blue stain) is confined to the sensory vesicle. (B) Dorso-lateral view of the head of a tailbud embryo electroporated with Meis_ciCNE10. Reporter expression (arrow) is localised to the sensory vesicle, adjacent to the otolith pigment cell (ot). (C, D) Lateral and dorsal views respectively of tailbud embryos electroporated with Meis_ciCNE1. In (C) reporter expression (arrow) is localised to the sensory vesicle, adjacent to the otolith pigment cell. In (D) reporter expression (arrow) is confined to the lateral tail epidermis of the right hand side.</p

Deletion analysis of Meis_ciCNE1 construct.

<p>(A) Scheme and quantification of the deletion constructs injected into zebrafish embryos and analysed for GFP expression at 48 hpf. The numbers in parentheses indicate the length of each construct. (B) Embryo injected with the full length CNE1 show GFP expression in the brain and in spinal cord motor- and interneurons. (C) Injection of DCNE1-3 drives GFP expression only in a few neurons in the head. (D) In the embryos injected with DCNE1-2+DCNE1-3 construct few motor- and interneurons are detected along the spinal cord. (E) In embryos injected with the construct DCNE1-4 GFP expression shows a pattern similar to full length, labelling both spinal cord interneurons and motor neurons as well as cells in the brain.</p

Summary of GFP reporter expression driven by ciCNEs at 48<i>Tol2</i> and co-injection strategies in zebrafish embryos.

<p>Summary of GFP reporter expression driven by ciCNEs at 48<i>Tol2</i> and co-injection strategies in zebrafish embryos.</p