Genomes and Genes
Gene Symbol: E(spl)mbeta-HLH
Description: Enhancer of split mbeta, helix-loop-helix
Alias: CG14548, Dm-mA, Dmel\CG14548, E(Spl) HLH-Mbeta, E(Spl)mbeta, E(spl), E(spl) mbeta, E(spl)-Mbeta, E(spl)-mbeta, E(spl)Mbeta, E(spl)beta, E(spl)mA, E(spl)mb, E(spl)mbeta, E(spl)mbeta}, HLH-mbeta, HLHMbeta, HLHmA, HLHmbeta, Mbeta, bHLHb34, m-beta, mbeta, enhancer of split mbeta, helix-loop-helix, CG14548-PA, E(spl) region transcript mbeta, E(spl)mbeta-HLH-PA, enhancer of split m-beta, enhancer of split mbeta, enhancer of split region transcript HLHmA, split locus enhancer protein mA
Species: fruit fly
- Ligoxygakis P, Bray S, Apidianakis Y, Delidakis C. Ectopic expression of individual E(spl) genes has differential effects on different cell fate decisions and underscores the biphasic requirement for notch activity in wing margin establishment in Drosophila. Development. 1999;126:2205-14 pubmed..Yet, the efficacy of this antagonism is quite distinct: E(spl)mbeta has the strongest vein suppression effect, whereas E(spl)m8 and E(spl)m7 are the most active bristle suppressors...
- Krejci A, Bray S. Notch activation stimulates transient and selective binding of Su(H)/CSL to target enhancers. Genes Dev. 2007;21:1322-7 pubmed..Unexpectedly, Su(H) occupancy was significantly and transiently increased following Notch activation, suggesting a more dynamic interaction with targets than hitherto proposed. ..
- 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..Our structural and functional analysis explains the rigid conservation of the WRPW motif, the sequence flexibility of eh1 motifs, and other aspects of repressor recognition by Gro in vivo. ..
- Nagel A, Maier D, Krauss S, Mezger M, Preiss A. Neurogenic phenotypes induced by RNA interference with bHLH genes of the Enhancer of split complex of Drosophila melanogaster. Genesis. 2004;39:105-14 pubmed..Surprisingly, interference with m3 results in a high rate of mortality which cannot be reproduced by genetic mutation. Most likely, m3 dsRNA interferes with unrelated genes involved in other aspects of embryonic development. ..
- Wech I, Bray S, Delidakis C, Preiss A. Distinct expression patterns of different enhancer of split bHLH genes during embryogenesis of Drosophila melanogaster. Dev Genes Evol. 1999;209:370-5 pubmed
- San Juán B, Baonza A. The bHLH factor deadpan is a direct target of Notch signaling and regulates neuroblast self-renewal in Drosophila. Dev Biol. 2011;352:70-82 pubmed publisher..We show that in addition to dpn, Notch signaling must be regulating other genes during this process that act redundantly with dpn. ..
- Ligoxygakis P, Yu S, Delidakis C, Baker N. A subset of notch functions during Drosophila eye development require Su(H) and the E(spl) gene complex. Development. 1998;125:2893-900 pubmed..Using misexpression experiments we also show that particular Enhancer-of-split bHLH genes can differ greatly in their contribution to lateral specification. ..
- de Celis J, Tyler D, de Celis J, Bray S. Notch signalling mediates segmentation of the Drosophila leg. Development. 1998;125:4617-26 pubmed..is locally activated in distal cells of each segment, as demonstrated by the restricted expression of the Enhancer of split mbeta gene, and is required for the formation of normal joints...
- Cooper M, Bray S. Frizzled regulation of Notch signalling polarizes cell fate in the Drosophila eye. Nature. 1999;397:526-30 pubmed
- Lai E, Tam B, Rubin G. Pervasive regulation of Drosophila Notch target genes by GY-box-, Brd-box-, and K-box-class microRNAs. Genes Dev. 2005;19:1067-80 pubmed..Collectively, these data establish insights into miRNA target recognition and demonstrate that the Notch signaling pathway is a major target of miRNA-mediated regulation in Drosophila. ..
- Maeder M, Polansky B, Robson B, EASTMAN D. Phylogenetic footprinting analysis in the upstream regulatory regions of the Drosophila enhancer of split genes. Genetics. 2007;177:1377-94 pubmed..The mgamma and mbeta regulatory regions are the most conserved of the bHLH genes...
- Cooper M, Tyler D, Furriols M, Chalkiadaki A, Delidakis C, Bray S. Spatially restricted factors cooperate with notch in the regulation of Enhancer of split genes. Dev Biol. 2000;221:390-403 pubmed..cross regulation between E(spl) genes, we have analysed the enhancer activity of sequences from the adjacent E(spl)mbeta, E(spl)mgamma and E(spl)mdelta genes and made comparisons to E(spl)m8...
- Duncan E, Dearden P. Evolution of a genomic regulatory domain: the role of gene co-option and gene duplication in the Enhancer of split complex. Genome Res. 2010;20:917-28 pubmed publisher..We discuss the consequence of this conserved domain for the recruitment of novel genes into the Notch signaling cascade. ..
- Wurmbach E, Wech I, Preiss A. The Enhancer of split complex of Drosophila melanogaster harbors three classes of Notch responsive genes. Mech Dev. 1999;80:171-80 pubmed..The two other non-bHLH genes within the locus, m1 and m6, are unrelated to the Notch pathway: m1 might code for a protease inhibitor of the Kazal family, and m6 for a novel peptide. ..
- de Celis Ibeas J, Bray S. Bowl is required downstream of Notch for elaboration of distal limb patterning. Development. 2003;130:5943-52 pubmed..This mechanism might be important in the diversification of arthropod limbs, because it explains how segmented tarsomeres could have arisen from an ancestral limb with an unsegmented tarsus. ..
- Lai E, Bodner R, Posakony J. The enhancer of split complex of Drosophila includes four Notch-regulated members of the bearded gene family. Development. 2000;127:3441-55 pubmed..Finally, we present our initial studies of the structure, expression and regulation of the newest member of the Brd gene family, Ocho, which is located in the recently identified Bearded Complex. ..
- Hao I, Green R, Dunaevsky O, Lengyel J, Rauskolb C. The odd-skipped family of zinc finger genes promotes Drosophila leg segmentation. Dev Biol. 2003;263:282-95 pubmed
- Zacharioudaki E, Magadi S, Delidakis C. bHLH-O proteins are crucial for Drosophila neuroblast self-renewal and mediate Notch-induced overproliferation. Development. 2012;139:1258-69 pubmed publisher..Therefore, E(spl) and Dpn act together to maintain the NB in a self-renewing state, a process in which they are assisted by Notch, which sustains expression of the E(spl) subset. ..
- Heitzler P, Bourouis M, Ruel L, Carteret C, Simpson P. Genes of the Enhancer of split and achaete-scute complexes are required for a regulatory loop between Notch and Delta during lateral signalling in Drosophila. Development. 1996;122:161-71 pubmed..Thus there is a regulatory loop between Notch and Delta that is under the transcriptional control of the E(spl)-C and AS-C genes. ..
- Giagtzoglou N, Koumbanakis K, Fullard J, Zarifi I, Delidakis C. Role of the Sc C terminus in transcriptional activation and E(spl) repressor recruitment. J Biol Chem. 2005;280:1299-305 pubmed..In vivo, the Sc C-terminal domain is required for E(spl) recruitment in an enhancer context-dependent fashion, suggesting that in some enhancers alternative interaction surfaces can be used to recruit E(spl) proteins. ..
- Hasson P, Egoz N, Winkler C, Volohonsky G, Jia S, Dinur T, et al. EGFR signaling attenuates Groucho-dependent repression to antagonize Notch transcriptional output. Nat Genet. 2005;37:101-5 pubmed..Thus, Gro is a new junction between signaling pathways, enabling EGFR signaling to antagonize transcriptional output by Notch and potentially other Gro-dependent pathways. ..
- Jennings B, Tyler D, Bray S. Target specificities of Drosophila enhancer of split basic helix-loop-helix proteins. Mol Cell Biol. 1999;19:4600-10 pubmed
- Tong X, Gui H, Jin F, Heck B, Lin P, Ma J, et al. Ataxin-1 and Brother of ataxin-1 are components of the Notch signalling pathway. EMBO Rep. 2011;12:428-35 pubmed publisher..Our results suggest that, in addition to their involvement in SCA1, ATXN1 and BOAT1 might participate in several Notch-controlled developmental and pathological processes. ..
- Maier D, Marte B, Schafer W, Yu Y, Preiss A. Drosophila evolution challenges postulated redundancy in the E(spl) gene complex. Proc Natl Acad Sci U S A. 1993;90:5464-8 pubmed..However, we find the entire E(spl) gene complex highly conserved during Drosophila evolution, indicating that all the genes as well as their organization are of functional importance. ..
- Okajima T, Irvine K. Regulation of notch signaling by o-linked fucose. Cell. 2002;111:893-904 pubmed
- Nellesen D, Lai E, Posakony J. Discrete enhancer elements mediate selective responsiveness of enhancer of split complex genes to common transcriptional activators. Dev Biol. 1999;213:33-53 pubmed
- Schrons H, Knust E, Campos Ortega J. The Enhancer of split complex and adjacent genes in the 96F region of Drosophila melanogaster are required for segregation of neural and epidermal progenitor cells. Genetics. 1992;132:481-503 pubmed..of the third chromosome and comprises at least seven structurally related genes, HLH-m delta, HLH-m gamma, HLH-m beta, HLH-m3, HLH-m5, HLH-m7 and E(spl)...
- Dobens L, Jaeger A, Peterson J, Raftery L. Bunched sets a boundary for Notch signaling to pattern anterior eggshell structures during Drosophila oogenesis. Dev Biol. 2005;287:425-37 pubmed
- Zarifi I, Kiparaki M, Koumbanakis K, Giagtzoglou N, Zacharioudaki E, Alexiadis A, et al. Essential roles of Da transactivation domains in neurogenesis and in E(spl)-mediated repression. Mol Cell Biol. 2012;32:4534-48 pubmed publisher..We present a mechanistic model on the interplay of these bHLH factors in the context of neural fate assignment. ..
- Luque C, Milan M. Growth control in the proliferative region of the Drosophila eye-head primordium: the elbow-noc gene complex. Dev Biol. 2007;301:327-39 pubmed..Thus, tight regulation of the size of the eye-head primordium by elbow and no ocelli is crucial for proper fate specification and generation of the adult structures. ..
- Fostier M, Evans D, Artavanis Tsakonas S, Baron M. Genetic characterization of the Drosophila melanogaster Suppressor of deltex gene: A regulator of notch signaling. Genetics. 1998;150:1477-85 pubmed..This corresponds to the period when the Notch protein is involved in refining the vein competent territories. Taken together, our data indicate a role for Su(dx) as a negative regulator of Notch function. ..
- Diaz Garcia S, Baonza A. Pattern reorganization occurs independently of cell division during Drosophila wing disc regeneration in situ. Proc Natl Acad Sci U S A. 2013;110:13032-7 pubmed publisher..We present evidence indicating that all of these processes occur even when cell division has been arrested. Our data also suggested that Wingless is not required during the early stages of disc regeneration. ..
- Housden B, Terriente Félix A, Bray S. Context-dependent enhancer selection confers alternate modes of notch regulation on argos. Mol Cell Biol. 2014;34:664-72 pubmed publisher..This is likely to be a general mechanism for enabling the wiring between these pathways to switch according to context. ..
- Bivik C, MacDonald R, Gunnar E, Mazouni K, Schweisguth F, Thor S. Control of Neural Daughter Cell Proliferation by Multi-level Notch/Su(H)/E(spl)-HLH Signaling. PLoS Genet. 2016;12:e1005984 pubmed publisher..These results point to a multi-level signaling model and may help shed light on the dichotomous proliferative role of Notch signaling in many other systems. ..
- Ronshaugen M, Levine M. Visualization of trans-homolog enhancer-promoter interactions at the Abd-B Hox locus in the Drosophila embryo. Dev Cell. 2004;7:925-32 pubmed..Such trans-homolog interactions might be a common mechanism of gene regulation in higher metazoans. ..
- Nagel A, Maier D, Preiss A. Su(H)-independent activity of hairless during mechano-sensory organ formation in Drosophila. Mech Dev. 2000;94:3-12 pubmed..Thereby, Hairless and numb may have partly redundant activities. This suggests that Notch-dependent binary cell fate specifications involve different sets of mediators depending on the cell type considered. ..
- Hartenstein V, Tepass U, Gruszynski deFeo E. Proneural and neurogenic genes control specification and Morphogenesis of stomatogastric nerve cell precursors in Drosophila. Dev Biol. 1996;173:213-27 pubmed
- Macdonald S, Pastinen T, Long A. The effect of polymorphisms in the enhancer of split gene complex on bristle number variation in a large wild-caught cohort of Drosophila melanogaster. Genetics. 2005;171:1741-56 pubmed..It may not be straightforward to extend the results of laboratory-based association studies to natural populations. ..
- Alifragis P, Poortinga G, Parkhurst S, Delidakis C. A network of interacting transcriptional regulators involved in Drosophila neural fate specification revealed by the yeast two-hybrid system. Proc Natl Acad Sci U S A. 1997;94:13099-104 pubmed..We investigated the structural requirements for some of these interactions by site-specific and deletion mutagenesis. ..
- Vaccari T, Duchi S, Cortese K, Tacchetti C, Bilder D. The vacuolar ATPase is required for physiological as well as pathological activation of the Notch receptor. Development. 2010;137:1825-32 pubmed publisher..The results also suggest that the ionic properties of the endosomal lumen might regulate Notch cleavage, providing a rationale for physiological as well as pathological endocytic control of Notch activity. ..
- Roignant J, Legent K, Janody F, Treisman J. The transcriptional co-factor Chip acts with LIM-homeodomain proteins to set the boundary of the eye field in Drosophila. Development. 2010;137:273-81 pubmed publisher..Loss-of-function studies support the model that Arrowhead and Lim1 act redundantly, using Chip as a co-factor, to prevent retinal differentiation in regions of the eye disc destined to become ventral head tissue. ..
- Maeda K, Takemura M, Umemori M, Adachi Yamada T. E-cadherin prolongs the moment for interaction between intestinal stem cell and its progenitor cell to ensure Notch signaling in adult Drosophila midgut. Genes Cells. 2008;13:1219-27 pubmed publisher..These findings reveal one of the normal N functions used to inhibit tumorigenesis through lowering of E-cad for proper midgut cell turnover. ..
- Mishra Gorur K, Rand M, Perez Villamil B, Artavanis Tsakonas S. Down-regulation of Delta by proteolytic processing. J Cell Biol. 2002;159:313-24 pubmed..The data support a model whereby Delta inactivation is essential for providing the critical ligand/receptor expression differential between neighboring cells in order to distinguish the signaling versus the receiving partner. ..
- Bonfini A, Wilkin M, Baron M. Reversible regulation of stem cell niche size associated with dietary control of Notch signalling. BMC Dev Biol. 2015;15:8 pubmed publisher..These findings reveal an unexpected reversible plasticity of the GSC niche whose responses provide an integrated read out of the physiological status of the fly that is modulated by diet and age. ..
- Parks A, Shalaby N, Muskavitch M. Notch and suppressor of Hairless regulate levels but not patterns of Delta expression in Drosophila. Genesis. 2008;46:265-75 pubmed publisher..We conclude that Notch pathway feedback regulation is unlikely to contribute to the generation of complementary patterns in the contexts examined. ..
- Maeder M, Megley C, EASTMAN D. Differential expression of the Enhancer of split genes in the developing Drosophila midgut. Hereditas. 2009;146:11-8 pubmed publisher..Two ancestral E(spl) genes, malpha and mbeta, are highly expressed and increase significantly at puparium formation, whereas another gene, mgamma, is expressed ..
- Macdonald S, Long A. Identifying signatures of selection at the enhancer of split neurogenic gene complex in Drosophila. Mol Biol Evol. 2005;22:607-19 pubmed publisher..All sites in regions apparently visible to various selective forces are candidates for future work to determine their phenotypic effects...
- Beam C, MOBERG K. The gang of four gene regulates growth and patterning of the developing Drosophila eye. Fly (Austin). 2010;4:104-16 pubmed..Genetic reduction of bru-3 suppresses phenotypes caused by gfr alleles, and like gfr alleles, overexpression of bru-3 depresses levels of Cic protein, indicating that overexpression of bru-3 is central to gfr mutant phenotypes. ..
- de Celis J. Expression and function of decapentaplegic and thick veins during the differentiation of the veins in the Drosophila wing. Development. 1997;124:1007-18 pubmed
- Wurmbach E, Preiss A. Deletion mapping in the Enhancer of split complex. Hereditas. 2014;151:159-68 pubmed publisher..Larger deletions, generated also by X-ray mutagenesis, uncover most of the E(spl)-C. The phenotypes of homozygous deficient embryos were analysed to characterize the respective loss of Notch signalling activity. ..
- Kobia F, Duchi S, Deflorian G, Vaccari T. Pharmacologic inhibition of vacuolar H+ ATPase reduces physiologic and oncogenic Notch signaling. Mol Oncol. 2014;8:207-20 pubmed publisher..Our data support V-ATPase inhibition as a novel therapeutic approach to counteract tumor growth via signaling pathways regulated at the endo-lysosomal level. ..
- Schlatter R, Maier D. The Enhancer of split and Achaete-Scute complexes of Drosophilids derived from simple ur-complexes preserved in mosquito and honeybee. BMC Evol Biol. 2005;5:67 pubmed..Here, the E(spl)-C consists of one bHLH (mbeta) and one Brd family member (malpha) in a head to head arrangement...
- Gigliani F, Longo F, Gaddini L, Battaglia P. Interactions among the bHLH domains of the proteins encoded by the Enhancer of split and achaete-scute gene complexes of Drosophila. Mol Gen Genet. 1996;251:628-34 pubmed..Also, the pattern of interactions of the bHLH domains of certain proteins encoded by the two gene complexes may explain their functional redundancy. ..
- Campos Ortega J. Genetic mechanisms of early neurogenesis in Drosophila melanogaster. J Physiol Paris. 1994;88:111-22 pubmed..The proneural genes appear to be the key elements in the regulation of the cellular decision. ..
- Classen A, Bunker B, Harvey K, Vaccari T, Bilder D. A tumor suppressor activity of Drosophila Polycomb genes mediated by JAK-STAT signaling. Nat Genet. 2009;41:1150-5 pubmed publisher..These findings show that PcG proteins can restrict growth directly by silencing mitogenic signaling pathways, shedding light on an epigenetic mechanism underlying tumor suppression. ..
- Capilla A, Johnson R, Daniels M, Benavente M, Bray S, Galindo M. Planar cell polarity controls directional Notch signaling in the Drosophila leg. Development. 2012;139:2584-93 pubmed publisher..Together, these results suggest that PCP coordinates the spatial activity of the Notch pathway by regulating endocytic trafficking of the receptor. ..
- Baker R, Kuehl J, Wilkinson G. The Enhancer of split complex arose prior to the diversification of schizophoran flies and is strongly conserved between Drosophila and stalk-eyed flies (Diopsidae). BMC Evol Biol. 2011;11:354 pubmed publisher..Results from this study provide numerous insights into the evolutionary history of the complex and will help refine the focus of studies examining the adaptive consequences of this gene expansion. ..
- Campos Ortega J. Mechanisms of early neurogenesis in Drosophila melanogaster. J Neurobiol. 1993;24:1305-27 pubmed
- Kaul A, Schuster E, Jennings B. The Groucho co-repressor is primarily recruited to local target sites in active chromatin to attenuate transcription. PLoS Genet. 2014;10:e1004595 pubmed publisher..Our results demonstrate that Gro is recruited to local sites by transcription factors to attenuate rather than silence gene expression by promoting histone deacetylation and polymerase pausing. ..
- Lai E, Burks C, Posakony J. The K box, a conserved 3' UTR sequence motif, negatively regulates accumulation of enhancer of split complex transcripts. Development. 1998;125:4077-88 pubmed..In support of this, we present sequence analyses that implicate genes of the iroquois Complex (Iro-C) and engrailed as additional targets of K box-mediated regulation. ..
- de Celis J, Barrio R. Function of the spalt/spalt-related gene complex in positioning the veins in the Drosophila wing. Mech Dev. 2000;91:31-41 pubmed..We suggest that the regulation of the iroquois and knirps gene complexes by Spalt and Spalt-related translates the Decapentaplegic morphogenetic gradient into precisely spaced pattern elements. ..
- Bang A, Bailey A, Posakony J. Hairless promotes stable commitment to the sensory organ precursor cell fate by negatively regulating the activity of the Notch signaling pathway. Dev Biol. 1995;172:479-94 pubmed
- Schaaf C, Misulovin Z, Gause M, Koenig A, Dorsett D. The Drosophila enhancer of split gene complex: architecture and coordinate regulation by notch, cohesin, and polycomb group proteins. G3 (Bethesda). 2013;3:1785-94 pubmed publisher..We posit that the E(spl)-C architecture dictates where cohesin and PcG complexes bind and act when they are recruited by as yet unidentified factors, thereby controlling the E(spl)-C as a coordinated domain. ..
- Baonza A, de Celis J, Garcia Bellido A. Relationships between extramacrochaetae and Notch signalling in Drosophila wing development. Development. 2000;127:2383-93 pubmed..We propose that at least during vein differentiation and wing margin formation, extramacrochaetae is regulated by Notch and collaborates with other Notch-downstream genes such as Enhancer of split-m(beta). ..
- Housden B, Perrimon N. Spatial and temporal organization of signaling pathways. Trends Biochem Sci. 2014;39:457-64 pubmed publisher..We consider the role of spatial and temporal aspects of different transduction pathways and then discuss how recently developed tools and approaches are helping to dissect the complex mechanisms linking pathway stimulation to output. ..
- del Alamo D, Mlodzik M. Self-modulation of Notch signaling during ommatidial development via the Roughened eye transcriptional repressor. Development. 2008;135:2895-904 pubmed publisher..Thus, our data suggest that Roe acts as a transcriptional repressor in a negative-feedback loop of the N pathway. ..
- Rand M, Bland C, Bond J. Methylmercury activates enhancer-of-split and bearded complex genes independent of the notch receptor. Toxicol Sci. 2008;104:163-76 pubmed publisher..MeHg transcriptional activation is partially mimicked by iodoacetamide but not by N-ethylmaleimide, two thiol-specific electrophiles, revealing a degree of specificity of cellular thiol targets in MeHg-induced transcriptional events. ..
- Sotillos S, de Celis J. Interactions between the Notch, EGFR, and decapentaplegic signaling pathways regulate vein differentiation during Drosophila pupal wing development. Dev Dyn. 2005;232:738-52 pubmed..Once dpp expression is initiated, Dpp and EGFR activities in the provein maintain each other and, in cooperation, determine vein cell differentiation. ..