Genomes and Genes
Gene Symbol: en
Alias: 153867_at, Apa, CG9015, Dmel\CG9015, EnR, Eng, Engr, Engrailed, Engrailed/Invected, en1, spa2, spt, engrailed, CG9015-PA, CG9015-PB, ENGRAILED, apigmented abdomen, en-PA, en-PB, erased, invected, sparse SGPs 2, spermatheca, transcript group V
Species: fruit fly
- Molnar C, Holguin H, Mayor F, Ruiz Gomez A, de Celis J. The G protein-coupled receptor regulatory kinase GPRK2 participates in Hedgehog signaling in Drosophila. Proc Natl Acad Sci U S A. 2007;104:7963-8 pubmed..Interestingly, the expression of Gprk2 in the wing disc is regulated in part by Smo, generating a positive feedback loop that maintains high Smo activity close to the anterior-posterior compartment boundary. ..
- Albert R, Othmer H. The topology of the regulatory interactions predicts the expression pattern of the segment polarity genes in Drosophila melanogaster. J Theor Biol. 2003;223:1-18 pubmed..The model gives important insights into the functioning of the segment polarity gene network, such as the crucial role of the wingless and sloppy paired genes, and the network's ability to correct errors in the pre-pattern. ..
- Wendler F, Franch Marro X, Vincent J. How does cholesterol affect the way Hedgehog works?. Development. 2006;133:3055-61 pubmed..However, the absence of the cholesterol adduct affects the spread of Hh within tissues. As we discuss here, the exact nature of this effect is controversial. ..
- DeVido S, Kwon D, Brown J, Kassis J. The role of Polycomb-group response elements in regulation of engrailed transcription in Drosophila. Development. 2008;135:669-76 pubmed publisher..Previous studies have shown that a 2 kb fragment located from -2.4 kb to -395 bp upstream of the Drosophila engrailed promoter contains a multipartite PRE that can mediate mini-white silencing and act as a PRE in an Ubx-reporter ..
- Hou H, Heffer A, Anderson W, Liu J, Bowler T, Pick L. Stripy Ftz target genes are coordinately regulated by Ftz-F1. Dev Biol. 2009;335:442-53 pubmed publisher..These are the earliest Ftz targets identified to date and all are coordinately regulated by Ftz-F1. Engrailed (En), the best-characterized Ftz/Ftz-F1 downstream target, is not an intermediate in regulation...
- Bolivar J, Pearson J, López Onieva L, González Reyes A. Genetic dissection of a stem cell niche: the case of the Drosophila ovary. Dev Dyn. 2006;235:2969-79 pubmed..We have identified a novel requirement for engrailed in the correct organization of the terminal filaments...
- Xu D, Li Y, Arcaro M, Lackey M, Bergmann A. The CARD-carrying caspase Dronc is essential for most, but not all, developmental cell death in Drosophila. Development. 2005;132:2125-34 pubmed..We also constructed double mutant flies for dronc and the apoptosis inhibitor diap1. dronc mutants can rescue the ovarian degeneration phenotype caused by diap1 mutations, confirming that dronc acts genetically downstream of diap1. ..
- Aguilar Hidalgo D, Domínguez Cejudo M, Amore G, Brockmann A, Lemos M, Cordoba A, et al. A Hh-driven gene network controls specification, pattern and size of the Drosophila simple eyes. Development. 2013;140:82-92 pubmed publisher..Our results highlight the role of the homeodomain transcription factor engrailed (en) both as a target and as a transcriptional repressor of hh signaling in the prospective interocellar region...
- Gettings M, Serman F, Rousset R, Bagnerini P, Almeida L, Noselli S. JNK signalling controls remodelling of the segment boundary through cell reprogramming during Drosophila morphogenesis. PLoS Biol. 2010;8:e1000390 pubmed publisher..by an anterior-to-posterior reprogramming mechanism involving de novo expression of the homeodomain protein Engrailed. Mixing is accompanied by stereotyped local cell intercalation, converting the segment boundary into a ..
- Dai P, Akimaru H, Ishii S. A hedgehog-responsive region in the Drosophila wing disc is defined by debra-mediated ubiquitination and lysosomal degradation of Ci. Dev Cell. 2003;4:917-28 pubmed..Thus, Debra defines the border of the Hh-responsive region in the A compartment by inducing the lysosomal degradation of Ci. ..
- Chanas G, Lavrov S, Iral F, Cavalli G, Maschat F. Engrailed and polyhomeotic maintain posterior cell identity through cubitus-interruptus regulation. Dev Biol. 2004;272:522-35 pubmedIn Drosophila, the subdivision into compartments requires the expression of engrailed (en) and hedgehog (hh) in the posterior cells and of cubitus-interruptus (ci) in the anterior cells...
- Rodriguez I. The dachsous gene, a member of the cadherin family, is required for Wg-dependent pattern formation in the Drosophila wing disc. Development. 2004;131:3195-206 pubmed
- Lebreton G, Faucher C, Cribbs D, Benassayag C. Timing of Wingless signalling distinguishes maxillary and antennal identities in Drosophila melanogaster. Development. 2008;135:2301-9 pubmed publisher..We characterised: (1) the action of Wg through ss selector function in distinguishing maxillary from antenna; and (2) its direct contribution to identity choice. ..
- Rojas Ríos P, Guerrero I, González Reyes A. Cytoneme-mediated delivery of hedgehog regulates the expression of bone morphogenetic proteins to maintain germline stem cells in Drosophila. PLoS Biol. 2012;10:e1001298 pubmed publisher..Hh production in cap cells, a type of niche support cells, is regulated by the Engrailed transcription factor...
- Pérez Garijo A, Martín F, Morata G. Caspase inhibition during apoptosis causes abnormal signalling and developmental aberrations in Drosophila. Development. 2004;131:5591-8 pubmed..We suggest that a similar process of uncoupling apoptosis initiation and cell death may occur during tumour formation in mammalian cells. ..
- Shu J, Li Y. A statistical fat-tail test of predicting regulatory regions in the Drosophila genome. Comput Biol Med. 2012;42:935-41 pubmed publisher..These two fatness coefficients may serve as valuable filtering indexes to predict CRMs experimentally. ..
- Callejo A, Torroja C, Quijada L, Guerrero I. Hedgehog lipid modifications are required for Hedgehog stabilization in the extracellular matrix. Development. 2006;133:471-83 pubmed..All these data show that the interaction of lipid-modified Hh with HSPG is important both for precise Hh spreading through the epithelium surface and for correct Hh reception. ..
- Sanchez L, Thieffry D. Segmenting the fly embryo: a logical analysis of the pair-rule cross-regulatory module. J Theor Biol. 2003;224:517-37 pubmed..model accounting for the ability of the pair-rule module to determine the formation of alternate juxtaposed Engrailed- and Wingless-expressing cells that form the (para)segmental boundaries...
- Ludwig M, Palsson A, Alekseeva E, Bergman C, Nathan J, Kreitman M. Functional evolution of a cis-regulatory module. PLoS Biol. 2005;3:e93 pubmed..Our findings have implications for understanding enhancer structure-function, mechanisms of speciation and computational identification of regulatory modules. ..
- Callejo A, Bilioni A, Mollica E, Gorfinkiel N, Andres G, Ibañez C, et al. Dispatched mediates Hedgehog basolateral release to form the long-range morphogenetic gradient in the Drosophila wing disk epithelium. Proc Natl Acad Sci U S A. 2011;108:12591-8 pubmed publisher..We also show that Dlp is needed in Hh-producing cells to allow for Hh release and that Ihog, which has been previously described as an Hh coreceptor, anchors Hh to the basolateral part of the disk epithelium. ..
- Kunttas Tatli E, Zhou M, Zimmerman S, Molinar O, Zhouzheng F, Carter K, et al. Destruction complex function in the Wnt signaling pathway of Drosophila requires multiple interactions between Adenomatous polyposis coli 2 and Armadillo. Genetics. 2012;190:1059-75 pubmed publisher..Finally, for some mutants, destruction complex function was dependent on APC1, suggesting that APC2 and APC1 may act cooperatively in the destruction complex. ..
- Walrad P, Hang S, Joseph G, Salas J, Gergen J. Distinct contributions of conserved modules to Runt transcription factor activity. Mol Biol Cell. 2010;21:2315-26 pubmed publisher..These results provide a foundation for further studies on the molecular interactions that contribute to the context-dependent properties of Runx proteins as developmental regulators. ..
- Gorfinkiel N, Sierra J, Callejo A, Ibañez C, Guerrero I. The Drosophila ortholog of the human Wnt inhibitor factor Shifted controls the diffusion of lipid-modified Hedgehog. Dev Cell. 2005;8:241-53 pubmed..We also show that human WIF inhibits Wg signaling in Drosophila without affecting the Hh pathway, indicating that different WIF family members might have divergent functions in each pathway. ..
- Wang W, Kidd B, Carroll S, Yoder J. Sexually dimorphic regulation of the Wingless morphogen controls sex-specific segment number in Drosophila. Proc Natl Acad Sci U S A. 2011;108:11139-44 pubmed publisher..We propose that dimorphic Wg regulation, in concert with monomorphic segment-specific programmed cell death, are the principal mechanisms of sculpting the sexually dimorphic abdomen of Drosophila. ..
- Ludwig M, Manu -, Kittler R, White K, Kreitman M. Consequences of eukaryotic enhancer architecture for gene expression dynamics, development, and fitness. PLoS Genet. 2011;7:e1002364 pubmed publisher..These results imply that seemingly redundant regulatory sequences beyond the minimal enhancer are necessary for robust gene expression and that "robustness" itself must be an evolved characteristic of the wild-type enhancer. ..
- Merabet S, Pradel J, Graba Y. Getting a molecular grasp on Hox contextual activity. Trends Genet. 2005;21:477-80 pubmed..A recent study identified novel Hox molecular partners, whose properties set a conceptual framework to understand how Hox proteins use and integrate contextual information. ..
- Bossing T, Brand A. Determination of cell fate along the anteroposterior axis of the Drosophila ventral midline. Development. 2006;133:1001-12 pubmed..Hedgehog and Lethal of scute activate Engrailed in these anterior cells...
- Estes P, Fulkerson E, Zhang Y. Identification of motifs that are conserved in 12 Drosophila species and regulate midline glia vs. neuron expression. Genetics. 2008;178:787-99 pubmed publisher..These results suggest short, highly conserved genomic sequences flanking Drosophila midline genes are indicative of functional regulatory regions and that small changes within these sequences can alter the expression pattern of a gene. ..
- Tautz D. Segmentation. Dev Cell. 2004;7:301-12 pubmed..An old concept of comparative anatomy, the enterocoele theory, is compatible with a single origin of segmentation mechanisms and could therefore provide a conceptual framework for assessing these molecular similarities. ..
- Liu Y, Cao X, Jiang J, Jia J. Fused-Costal2 protein complex regulates Hedgehog-induced Smo phosphorylation and cell-surface accumulation. Genes Dev. 2007;21:1949-63 pubmed..Our data suggest that Cos2-Smo interaction blocks Hh-induced Smo phosphorylation, and that Fu promotes Smo phosphorylation by antagonizing Cos2. ..
- Joly W, Mugat B, Maschat F. Engrailed controls the organization of the ventral nerve cord through frazzled regulation. Dev Biol. 2007;301:542-54 pubmed..Here we show that Engrailed, a homeodomain transcription factor known to be involved in the establishment of neuroblast identity, is also ..
- Schuettengruber B, Ganapathi M, Leblanc B, Portoso M, Jaschek R, Tolhuis B, et al. Functional anatomy of polycomb and trithorax chromatin landscapes in Drosophila embryos. PLoS Biol. 2009;7:e13 pubmed publisher..Furthermore, several DNA sequence features discriminate between PcG- and TRX-N-bound regions, indicating that underlying DNA sequence contains critical information to drive PREs and TREs towards silencing or activation. ..
- Kim S, Shim H, Jeon B, Choi W, Hur M, Girton J, et al. The pleiohomeotic functions as a negative regulator of Drosophila even-skipped gene during embryogenesis. Mol Cells. 2011;32:549-54 pubmed publisher..Our results indicated that engrailed and even-skipped genes were misexpressed in pho mutant embryos, which caused embryonic segment defects.
- Urbach R, Technau G. Segment polarity and DV patterning gene expression reveals segmental organization of the Drosophila brain. Development. 2003;130:3607-20 pubmed..brain neuroblasts, we carried out a comprehensive analysis of the expression of segment polarity genes (engrailed, wingless, hedgehog, gooseberry distal, mirror) and DV patterning genes (muscle segment homeobox, intermediate ..
- Takaesu N, Herbig E, Zhitomersky D, O Connor M, Newfeld S. DNA-binding domain mutations in SMAD genes yield dominant-negative proteins or a neomorphic protein that can activate WG target genes in Drosophila. Development. 2005;132:4883-94 pubmed..From a larger perspective, our study shows that the genetic characterization of missense mutations, particularly in modular proteins, requires experimental verification. ..
- Croker J, Ziegenhorn S, Holmgren R. Regulation of the Drosophila transcription factor, Cubitus interruptus, by two conserved domains. Dev Biol. 2006;291:368-81 pubmed..Analysis of the amino acid sequence of this domain identifies 11 perfectly conserved serines and one tyrosine. We propose that this region may be modified, possibly by phosphorylation, to regulate Ci nuclear import. ..
- Fay A, Misulovin Z, Li J, Schaaf C, Gause M, Gilmour D, et al. Cohesin selectively binds and regulates genes with paused RNA polymerase. Curr Biol. 2011;21:1624-34 pubmed publisher..Our findings argue that cohesin and pausing factors are recruited independently to the same genes, perhaps by GAF and the GT repeats, and that their combined action determines the level of actively elongating RNA polymerase. ..
- Zhou Q, Kalderon D. Hedgehog activates fused through phosphorylation to elicit a full spectrum of pathway responses. Dev Cell. 2011;20:802-14 pubmed publisher..In this model, Smo acts like many transmembrane receptors associated with cytoplasmic kinases, such that pathway activation is mediated by kinase oligomerization and trans-phosphorylation. ..
- Glise B, Miller C, Crozatier M, Halbisen M, Wise S, Olson D, et al. Shifted, the Drosophila ortholog of Wnt inhibitory factor-1, controls the distribution and movement of Hedgehog. Dev Cell. 2005;8:255-66 pubmed..Our data further indicate that Shf interacts with Hh and the heparan sulfate proteoglycans. Therefore, we propose that Shf stabilizes the interaction between Hh and the proteoglycans, an unexpected role for a member of the WIF-1 family. ..
- Millard T, Martin P. Dynamic analysis of filopodial interactions during the zippering phase of Drosophila dorsal closure. Development. 2008;135:621-6 pubmed publisher..fly in which RFP-Moesin and GFP-Moesin are expressed in mutually exclusive stripes within each segment using the engrailed and patched promoters...
- Smith Bolton R, Worley M, Kanda H, Hariharan I. Regenerative growth in Drosophila imaginal discs is regulated by Wingless and Myc. Dev Cell. 2009;16:797-809 pubmed publisher..This system is conducive to forward genetic screens, enabling an unbiased search for genes that regulate both the extent of and the capacity for regeneration. ..
- Domínguez Giménez P, Brown N, Martin Bermudo M. Integrin-ECM interactions regulate the changes in cell shape driving the morphogenesis of the Drosophila wing epithelium. J Cell Sci. 2007;120:1061-71 pubmed..Finally, we show that the ECM has an instructive rather than a structural role, because inhibition of Raf reverses the cell shape changes caused by perturbing integrins. ..
- Delon I, Payre F. Evolution of larval morphology in flies: get in shape with shavenbaby. Trends Genet. 2004;20:305-13 pubmed
- Zheng X, Mann R, Sever N, Beachy P. Genetic and biochemical definition of the Hedgehog receptor. Genes Dev. 2010;24:57-71 pubmed publisher..On the basis of their joint roles in ligand binding, signal transduction, and receptor trafficking, we conclude that Ihog and Ptc together constitute the Drosophila Hh receptor. ..
- Kwon D, Mucci D, Langlais K, Americo J, DeVido S, Cheng Y, et al. Enhancer-promoter communication at the Drosophila engrailed locus. Development. 2009;136:3067-75 pubmed publisher..which gene to activate? We have used homing P[en] constructs to study the enhancer-promoter communication at the engrailed locus...
- Hendriksen J, Fagotto F, van der Velde H, van Schie M, Noordermeer J, Fornerod M. RanBP3 enhances nuclear export of active (beta)-catenin independently of CRM1. J Cell Biol. 2005;171:785-97 pubmed..We conclude that RanBP3 is a direct export enhancer for beta-catenin, independent of its role as a CRM1-associated nuclear export cofactor. ..
- Oktaba K, Gutierrez L, Gagneur J, Girardot C, Sengupta A, Furlong E, et al. Dynamic regulation by polycomb group protein complexes controls pattern formation and the cell cycle in Drosophila. Dev Cell. 2008;15:877-89 pubmed publisher..Analysis of cell cycle regulators indicates that the PcG system also dynamically modulates the expression levels of certain genes, providing a possible explanation for the tumor phenotype of PcG mutants. ..
- Eugster C, Panàkovà D, Mahmoud A, Eaton S. Lipoprotein-heparan sulfate interactions in the Hh pathway. Dev Cell. 2007;13:57-71 pubmed..They further suggest that the complement of proteins present on lipoprotein particles can regulate the activity of morphogens. ..
- Claret S, Sanial M, Plessis A. Evidence for a novel feedback loop in the Hedgehog pathway involving Smoothened and Fused. Curr Biol. 2007;17:1326-33 pubmed
- Nekrasov M, Klymenko T, Fraterman S, Papp B, Oktaba K, Kocher T, et al. Pcl-PRC2 is needed to generate high levels of H3-K27 trimethylation at Polycomb target genes. EMBO J. 2007;26:4078-88 pubmed..Pcl-PRC2 is thus the HMTase that generates the high levels of H3-K27 trimethylation in Polycomb target genes that are needed to maintain a Polycomb-repressed chromatin state. ..
- Vincent S, Perrimon N, Axelrod J. Hedgehog and Wingless stabilize but do not induce cell fate during Drosophila dorsal embryonic epidermal patterning. Development. 2008;135:2767-75 pubmed publisher..The combination of independent progression of cell identity and arrest of progression by signals facilitates accurate patterning of an extremely plastic developing epidermis. ..
- Urbach R, Schnabel R, Technau G. The pattern of neuroblast formation, mitotic domains and proneural gene expression during early brain development in Drosophila. Development. 2003;130:3589-606 pubmed
- Chanas G, Maschat F. Tissue specificity of hedgehog repression by the Polycomb group during Drosophila melanogaster development. Mech Dev. 2005;122:975-87 pubmed..the secreted protein Hedgehog, which is only expressed in P compartments and which is a key effector of the Engrailed transcription factor...
- Jennings B, Pickles L, Wainwright S, Roe S, Pearl L, Ish Horowicz D. Molecular recognition of transcriptional repressor motifs by the WD domain of the Groucho/TLE corepressor. Mol Cell. 2006;22:645-55 pubmed..short peptide sequences, including a C-terminal WRPW/Y motif (Hairy/Hes/Runx) and internal eh1 motifs (FxIxxIL; Engrailed/Goosecoid/Pax/Nkx)...
- Dawber R, Hebbes S, Herpers B, Docquier F, van den Heuvel M. Differential range and activity of various forms of the Hedgehog protein. BMC Dev Biol. 2005;5:21 pubmed
- Schwartz Y, Kahn T, Nix D, Li X, Bourgon R, Biggin M, et al. Genome-wide analysis of Polycomb targets in Drosophila melanogaster. Nat Genet. 2006;38:700-5 pubmed..PcG targets are highly enriched in genes encoding transcription factors, but they also include genes coding for receptors, signaling proteins, morphogens and regulators representing all major developmental pathways. ..
- Gallet A, Ruel L, Staccini Lavenant L, Therond P. Cholesterol modification is necessary for controlled planar long-range activity of Hedgehog in Drosophila epithelia. Development. 2006;133:407-18 pubmed..We conclude that, as in vertebrates, cholesterol modification is essential for controlled long-range Hh signalling in Drosophila. ..
- Deshpande G, Schedl P. HMGCoA reductase potentiates hedgehog signaling in Drosophila melanogaster. Dev Cell. 2005;9:629-38 pubmed..Consistent with this model, there are substantial germ cell migration defects in trans combinations between hmgcr and mutations in different components of the hh pathway. ..
- Zhao Y, Tong C, Jiang J. Hedgehog regulates smoothened activity by inducing a conformational switch. Nature. 2007;450:252-8 pubmed..Hence, by employing multiple Arg clusters as inhibitory elements counteracted by differential phosphorylation, SMO acts as a rheostat to translate graded HH signals into distinct responses. ..
- Wang X, Lee C, Gilmour D, Gergen J. Transcription elongation controls cell fate specification in the Drosophila embryo. Genes Dev. 2007;21:1031-6 pubmed..The finding that NELF also associates with the promoter regions of wingless (wg) and engrailed (en), two other pivotal targets of the pair-rule transcription factors, strongly suggests that developmentally ..
- Gambetta M, Oktaba K, Muller J. Essential role of the glycosyltransferase sxc/Ogt in polycomb repression. Science. 2009;325:93-6 pubmed publisher..Polycomb repression appears to be a critical function of Sxc/Ogt in Drosophila and may be mediated by the glycosylation of Polyhomeotic. ..
- López Onieva L, Fernández Miñán A, González Reyes A. Jak/Stat signalling in niche support cells regulates dpp transcription to control germline stem cell maintenance in the Drosophila ovary. Development. 2008;135:533-40 pubmed publisher..Our results provide strong evidence for a model in which Jak/Stat signalling in somatic support cells regulates dpp transcription to define niche size and to maintain the adjacent germline stem cells in an undifferentiated state. ..
- Estella C, Rieckhof G, Calleja M, Morata G. The role of buttonhead and Sp1 in the development of the ventral imaginal discs of Drosophila. Development. 2003;130:5929-41 pubmed..cells expressing btd generate their own signalling system, including the establishment of a sharp boundary of engrailed expression, and the local activation of the wingless and decapentaplegic genes...
- McEwen D, Peifer M. Puckered, a Drosophila MAPK phosphatase, ensures cell viability by antagonizing JNK-induced apoptosis. Development. 2005;132:3935-46 pubmed..However, if cell death is prevented, JNK activation can trigger tissue overgrowth. Thus, MKPs are key regulators of the delicate balance between proliferation, differentiation and apoptosis during development. ..
- Vied C, Kalderon D. Hedgehog-stimulated stem cells depend on non-canonical activity of the Notch co-activator Mastermind. Development. 2009;136:2177-86 pubmed publisher..Loss of Mam reduces the expression of a Hh pathway reporter in FSCs but not in wing discs, suggesting that Mam might enhance Hh signaling specifically in stem cells of the Drosophila ovary. ..
- Gryzik T, Müller H. FGF8-like1 and FGF8-like2 encode putative ligands of the FGF receptor Htl and are required for mesoderm migration in the Drosophila gastrula. Curr Biol. 2004;14:659-67 pubmed..Our results suggest that FGF8-like1 and FGF8-like2 represent ligands of the Htl FGF receptor. ..
- Zhang C, Williams E, Guo Y, Lum L, Beachy P. Extensive phosphorylation of Smoothened in Hedgehog pathway activation. Proc Natl Acad Sci U S A. 2004;101:17900-7 pubmed..Our studies confirm and extend previous studies showing a positive effect for cAMP-dependent protein kinase and uncover a positive role for casein kinase 1alpha in Hh pathway activation. ..
- Ruel L, Rodriguez R, Gallet A, Lavenant Staccini L, Therond P. Stability and association of Smoothened, Costal2 and Fused with Cubitus interruptus are regulated by Hedgehog. Nat Cell Biol. 2003;5:907-13 pubmed..We propose that the association of the Cos2 protein complex with Smo at the plasma membrane controls the stability of the complex and allows Ci activation, eliciting its nuclear translocation. ..
- Jaeger J, Reinitz J. On the dynamic nature of positional information. Bioessays. 2006;28:1102-11 pubmed..Based on this analysis, we propose a revised French Flag, which incorporates the dynamic, feedback-driven nature of pattern formation in the Drosophila blastoderm. ..
- Andrioli L, Oberstein A, Corado M, Yu D, Small S. Groucho-dependent repression by sloppy-paired 1 differentially positions anterior pair-rule stripes in the Drosophila embryo. Dev Biol. 2004;276:541-51 pubmed..to the precise spatial arrangement of anterior pair-rule stripe borders required for expression of the first engrailed stripe and the formation of the mandibular segment...
- Swantek D, Gergen J. Ftz modulates Runt-dependent activation and repression of segment-polarity gene transcription. Development. 2004;131:2281-90 pubmed..find that Ftz modulates the Runt-dependent regulation of the segment-polarity genes wingless (wg) and engrailed (en). However, in the case of en the combination of Runt + Ftz gives activation...