-
Články
- Časopisy
- Kurzy
- Témy
- Kongresy
- Videa
- Podcasty
Antagonism Versus Cooperativity with TALE Cofactors at the Base of the Functional Diversification of Hox Protein Function
Extradenticle (Exd) and Homothorax (Hth) function as positive transcriptional cofactors of Hox proteins, helping them to bind specifically their direct targets. The posterior Hox protein Abdominal-B (Abd-B) does not require Exd/Hth to bind DNA; and, during embryogenesis, Abd-B represses hth and exd transcription. Here we show that this repression is necessary for Abd-B function, as maintained Exd/Hth expression results in transformations similar to those observed in loss-of-function Abd-B mutants. We characterize the cis regulatory module directly regulated by Abd-B in the empty spiracles gene and show that the Exd/Hth complex interferes with Abd-B binding to this enhancer. Our results suggest that this novel Exd/Hth function does not require the complex to bind DNA and may be mediated by direct Exd/Hth binding to the Abd-B homeodomain. Thus, in some instances, the main positive cofactor complex for anterior Hox proteins can act as a negative factor for the posterior Hox protein Abd-B. This antagonistic interaction uncovers an alternative way in which MEIS and PBC cofactors can modulate Abd-B like posterior Hox genes during development.
Vyšlo v časopise: Antagonism Versus Cooperativity with TALE Cofactors at the Base of the Functional Diversification of Hox Protein Function. PLoS Genet 9(2): e32767. doi:10.1371/journal.pgen.1003252
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1003252Souhrn
Extradenticle (Exd) and Homothorax (Hth) function as positive transcriptional cofactors of Hox proteins, helping them to bind specifically their direct targets. The posterior Hox protein Abdominal-B (Abd-B) does not require Exd/Hth to bind DNA; and, during embryogenesis, Abd-B represses hth and exd transcription. Here we show that this repression is necessary for Abd-B function, as maintained Exd/Hth expression results in transformations similar to those observed in loss-of-function Abd-B mutants. We characterize the cis regulatory module directly regulated by Abd-B in the empty spiracles gene and show that the Exd/Hth complex interferes with Abd-B binding to this enhancer. Our results suggest that this novel Exd/Hth function does not require the complex to bind DNA and may be mediated by direct Exd/Hth binding to the Abd-B homeodomain. Thus, in some instances, the main positive cofactor complex for anterior Hox proteins can act as a negative factor for the posterior Hox protein Abd-B. This antagonistic interaction uncovers an alternative way in which MEIS and PBC cofactors can modulate Abd-B like posterior Hox genes during development.
Zdroje
1. PearsonJC, LemonsD, McGinnisW (2005) Modulating Hox gene functions during animal body patterning. Nat Rev Genet 6 : 893–904.
2. HueberSD, WeillerGF, DjordjevicMA, FrickeyT (2010) Improving Hox protein classification across the major model organisms. PLoS ONE 5: e10820 doi:10.1371/journal.pone.0010820.
3. MerabetS, HudryB, SaadaouiM, GrabaY (2009) Classification of sequence signatures: a guide to Hox protein function. Bioessays 31 : 500–511.
4. HombríaJC-G, RivasML, SotillosS (2009) Genetic control of morphogenesis - Hox induced organogenesis of the posterior spiracles. Int J Dev Biol 53 : 1349–1358.
5. HuN, Castelli-GairJ (1999) Study of the posterior spiracles of Drosophila as a model to understand the genetic and cellular mechanisms controlling morphogenesis. Developmental Biology 214 : 197–210.
6. BradleyPL, HabermanAS, AndrewDJ (2001) Organ formation in Drosophila: specification and morphogenesis of the salivary gland. Bioessays 23 : 901–911.
7. EstellaC, RieckhofG, CallejaM, MorataG (2003) The role of buttonhead and Sp1 in the development of the ventral imaginal discs of Drosophila. Development 130 : 5929–5941.
8. VachonG, CohenB, PfeifleC, McGuffinME, BotasJ, et al. (1992) Homeotic genes of the Bithorax complex repress limb development in the abdomen of the Drosophila embryo through the target gene Distal-less. Cell 71 : 437–450.
9. MannRS, LelliKM, JoshiR (2009) Hox specificity unique roles for cofactors and collaborators. Curr Top Dev Biol 88 : 63–101.
10. EkkerSC, JacksonDG, von KesslerDP, SunBI, YoungKE, et al. (1994) The degree of variation in DNA sequence recognition among four Drosophila homeotic proteins. EMBO J 13 : 3551–3560.
11. NoyesMB, ChristensenRG, WakabayashiA, StormoGD, BrodskyMH, et al. (2008) Analysis of homeodomain specificities allows the family-wide prediction of preferred recognition sites. Cell 133 : 1277–1289.
12. MannRS (1995) The specificity of homeotic gene function. Bioessays 17 : 855–863.
13. MoensCB, SelleriL (2006) Hox cofactors in vertebrate development. Dev Biol 291 : 193–206.
14. van DijkMA, MurreC (1994) extradenticle raises the DNA binding specificity of homeotic selector gene products. Cell 78 : 617–624.
15. RyooHD, MartyT, CasaresF, AffolterM, MannRS (1999) Regulation of Hox target genes by a DNA bound Homothorax/Hox/Extradenticle complex. Development 126 : 5137–5148.
16. MerabetS, SaadaouiM, SambraniN, HudryB, PradelJ, et al. (2007) A unique Extradenticle recruitment mode in the Drosophila Hox protein Ultrabithorax. Proc Natl Acad Sci U S A 104 : 16946–16951.
17. RieckhofGE, CasaresF, RyooHD, Abu-ShaarM, MannRS (1997) Nuclear translocation of extradenticle requires homothorax, which encodes an extradenticle-related homeodomain protein. Cell 91 : 171–183.
18. PeiferM, WieschausE (1990) Mutations in the Drosophila gene extradenticle affect the way specific homeo domain proteins regulate segmental identity. Genes Dev 4 : 1209–1223.
19. CasanovaJ, Sanchez-HerreroE, MorataG (1986) Identification and characterization of a parasegment specific regulatory element of the abdominal-B gene of Drosophila. Cell 47 : 627–636.
20. CelnikerSE, SharmaS, KeelanDJ, LewisEB (1990) The molecular genetics of the bithorax complex of Drosophila: cis-regulation in the Abdominal-B domain. Embo J 9 : 4277–4286.
21. DeLorenziM, AliN, SaariG, HenryC, WilcoxM, et al. (1988) Evidence that the Abdominal-B r element function is conferred by a trans-regulatory homeoprotein. Embo J 7 : 3223–3231.
22. ZavortinkM, SakonjuS (1989) The morphogenetic and regulatory functions of the Drosophila Abdominal-B gene are encoded in overlapping RNAs transcribed from separate promoters. Genes Dev 3 : 1969–1981.
23. BouletAM, LloydA, SakonjuS (1991) Molecular definition of the morphogenetic and regulatory functions and the cis-regulatory elements of the Drosophila Abd-B homeotic gene. Development 111 : 393–405.
24. Sánchez-HerreroE, VernósI, MarcoR, MorataG (1985) Genetic organisation of the Drosophila bithorax complex. Nature 313 : 108–113.
25. JonesB, McGinnisW (1993) The regulation of empty spiracles by Abdominal-B mediates an abdominal segment identity function. Genes Dev 7 : 229–240.
26. KuzioraMA (1993) Abdominal-B protein isoforms exhibit distinct cuticular transformations and regulatory activities when ectopically expressed in Drosophila embryos. Mech Dev 42 : 125–137.
27. LamkaML, BouletAM, SakonjuS (1992) Ectopic expression of UBX and ABD-B proteins during Drosophila embryogenesis: competition, not a functional hierarchy, explains phenotypic suppression. Development 116 : 841–854.
28. AzpiazuN, MorataG (1998) Functional and regulatory interactions between Hox and extradenticle genes. Genes Dev 12 : 261–273.
29. KurantE, PaiCY, SharfR, HalachmiN, SunYH, et al. (1998) Dorsotonals/homothorax, the Drosophila homologue of meis1, interacts with extradenticle in patterning of the embryonic PNS. Development 125 : 1037–1048.
30. RauskolbC, PeiferM, WieschausE (1993) extradenticle, a regulator of homeotic gene activity, is a homolog of the homeobox-containing human proto-oncogene pbx1. Cell 74 : 1101–1112.
31. Castelli-GairJ, GreigS, MicklemG, AkamM (1994) Dissecting the temporal requirements for homeotic gene function. Development 120 : 1983–1995.
32. NoroB, CuliJ, McKayDJ, ZhangW, MannRS (2006) Distinct functions of homeodomain-containing and homeodomain-less isoforms encoded by homothorax. Genes Dev 20 : 1636–1650.
33. ShenWF, RozenfeldS, LawrenceHJ, LargmanC (1997) The Abd-B-like Hox homeodomain proteins can be subdivided by the ability to form complexes with Pbx1a on a novel DNA target. J Biol Chem 272 : 8198–8206.
34. Garcia-FernandezJ (2005) Hox, ParaHox, ProtoHox: facts and guesses. Heredity 94 : 145–152.
35. WilliamsTM, SelegueJE, WernerT, GompelN, KoppA, et al. (2008) The regulation and evolution of a genetic switch controlling sexually dimorphic traits in Drosophila. Cell 134 : 610–623.
36. JeongS, RokasA, CarrollSB (2006) Regulation of body pigmentation by the Abdominal-B Hox protein and its gain and loss in Drosophila evolution. Cell 125 : 1387–1399.
37. LovegroveB, SimoesS, RivasML, SotillosS, JohnsonK, et al. (2006) Coordinated control of cell adhesion, polarity, and cytoskeleton underlies Hox-induced organogenesis in Drosophila. Curr Biol 16 : 2206–2216.
38. SambraniN, HudryB, MerabetS, GrabaY (2013) Distinct molecular strategies for Hox-mediated limb suppression in Drosophila: from cooperativity to dispensability/antagonism in TALE partnership. PLoS Genet in press.
39. EstradaB, Sanchez-HerreroE (2001) The Hox gene Abdominal-B antagonizes appendage development in the genital disc of Drosophila. Development 128 : 331–339.
40. StruhlG, WhiteRAH (1985) Regulation of the Ultrabithorax gene of Drosophila by the other bithorax complex genes. Cell 43 : 507–519.
41. Miguel-AliagaI, ThorS (2004) Segment-specific prevention of pioneer neuron apoptosis by cell-autonomous, postmitotic Hox gene activity. Development 131 : 6093–6105.
42. GalantR, WalshCM, CarrollSB (2002) Hox repression of a target gene: extradenticle-independent, additive action through multiple monomer binding sites. Development 129 : 3115–3126.
43. LemonsD, McGinnisW (2006) Genomic evolution of Hox gene clusters. Science 313 : 1918–1922.
44. LaRonde-LeBlancNA, WolbergerC (2003) Structure of HoxA9 and Pbx1 bound to DNA: Hox hexapeptide and DNA recognition anterior to posterior. Genes Dev 17 : 2060–2072.
45. ShenWF, RozenfeldS, KwongA, Kom vesLG, LawrenceHJ, et al. (1999) HOXA9 forms triple complexes with PBX2 and MEIS1 in myeloid cells. Mol Cell Biol 19 : 3051–3061.
46. GordonJA, HassanMQ, SainiS, MontecinoM, van WijnenAJ, et al. (2010) Pbx1 represses osteoblastogenesis by blocking Hoxa10-mediated recruitment of chromatin remodeling factors. Mol Cell Biol 30 : 3531–3541.
47. BromleighVC, FreedmanLP (2000) p21 is a transcriptional target of HOXA10 in differentiating myelomonocytic cells. Genes Dev 14 : 2581–2586.
48. SlatteryM, RileyT, LiuP, AbeN, Gomez-AlcalaP, et al. (2011) Cofactor binding evokes latent differences in DNA binding specificity between Hox proteins. Cell 147 : 1270–1282.
49. ChangCP, BrocchieriL, ShenWF, LargmanC, ClearyML (1996) Pbx modulation of Hox homeodomain amino-terminal arms establishes different DNA-binding specificities across the Hox locus. Mol Cell Biol 16 : 1734–1745.
50. ShenWF, MontgomeryJC, RozenfeldS, MoskowJJ, LawrenceHJ, et al. (1997) AbdB-like Hox proteins stabilize DNA binding by the Meis1 homeodomain proteins. Mol Cell Biol 17 : 6448–6458.
51. ShenWF, ChangCP, RozenfeldS, SauvageauG, HumphriesRK, et al. (1996) Hox homeodomain proteins exhibit selective complex stabilities with Pbx and DNA. Nucleic Acids Res 24 : 898–906.
52. ZhaiZ, YangX, LohmannI (2011) Functional dissection of the Hox protein Abdominal-B in Drosophila cell culture. Biochem Biophys Res Commun 414 : 761–766.
53. CareyMF, PetersonCL, SmaleST (2009) Chromatin immunoprecipitation (ChIP). Cold Spring Harb Protoc 2009: pdb prot5279.
54. SandmannT, JakobsenJS, FurlongEE (2006) ChIP-on-chip protocol for genome-wide analysis of transcription factor binding in Drosophila melanogaster embryos. Nat Protoc 1 : 2839–2855.
55. Abu-ShaarM, RyooHD, MannRS (1999) Control of the nuclear localization of Extradenticle by competing nuclear import and export signals. Genes Dev 13 : 935–945.
Štítky
Genetika Reprodukčná medicína
Článek MSH3 Polymorphisms and Protein Levels Affect CAG Repeat Instability in Huntington's Disease MiceČlánek Yemanuclein and HIRA Cooperate for Assembly of H3.3-Containing Nucleosomes in the Male Pronucleus
Článok vyšiel v časopisePLOS Genetics
Najčítanejšie tento týždeň
2013 Číslo 2- Gynekologové a odborníci na reprodukční medicínu se sejdou na prvním virtuálním summitu
- Je „freeze-all“ pro všechny? Odborníci na fertilitu diskutovali na virtuálním summitu
-
Všetky články tohto čísla
- Complex Inheritance of Melanoma and Pigmentation of Coat and Skin in Grey Horses
- A Meta-Analysis of Thyroid-Related Traits Reveals Novel Loci and Gender-Specific Differences in the Regulation of Thyroid Function
- Genetic Landscape of Open Chromatin in Yeast
- Deleterious Alleles in the Human Genome Are on Average Younger Than Neutral Alleles of the Same Frequency
- Age-Dependent Transition from Cell-Level to Population-Level Control in Murine Intestinal Homeostasis Revealed by Coalescence Analysis
- Next-Generation Sequencing Identifies the Danforth's Short Tail Mouse Mutation as a Retrotransposon Insertion Affecting Expression
- ImmunoChip Study Implicates Antigen Presentation to T Cells in Narcolepsy
- Massive Mitochondrial Gene Transfer in a Parasitic Flowering Plant Clade
- Comment on “Genomic Hypomethylation in the Human Germline Associates with Selective Structural Mutability in the Human Genome”
- The Prefoldin Bud27 Mediates the Assembly of the Eukaryotic RNA Polymerases in an Rpb5-Dependent Manner
- Genetic Determinants of Trabecular and Cortical Volumetric Bone Mineral Densities and Bone Microstructure
- Encodes a Novel and -Genus-Specific Regulator of Photoperiodic Flowering in Rice
- Only One Isoform of CTP Synthase Forms the Cytoophidium
- Mechanisms Involved in the Functional Divergence of Duplicated GroEL Chaperonins in DK1622
- A Genome-Wide RNAi Screen in Identifies the Nicotinic Acetylcholine Receptor Subunit ACR-7 as an Antipsychotic Drug Target
- Autophagy Induction Is a Tor- and Tp53-Independent Cell Survival Response in a Zebrafish Model of Disrupted Ribosome Biogenesis
- Ancient DNA Reveals Prehistoric Gene-Flow from Siberia in the Complex Human Population History of North East Europe
- Inflammation-Mediated Genetic and Epigenetic Alterations Drive Cancer Development in the Neighboring Epithelium upon Stromal Abrogation of TGF-β Signaling
- MicroRNA-3148 Modulates Allelic Expression of Toll-Like Receptor 7 Variant Associated with Systemic Lupus Erythematosus
- RNAi–Based Functional Profiling of Loci from Blood Lipid Genome-Wide Association Studies Identifies Genes with Cholesterol-Regulatory Function
- CELF Family RNA–Binding Protein UNC-75 Regulates Two Sets of Mutually Exclusive Exons of the Gene in Neuron-Specific Manners in
- Coordination of Chromatid Separation and Spindle Elongation by Antagonistic Activities of Mitotic and S-Phase CDKs
- The Ubiquitin Ligase Subunit Acts in Target Tissue to Restrict Tracheal Terminal Cell Branching and Hypoxic-Induced Gene Expression
- Mitotic Evolution of Shows a Stable Core Genome but Recombination in Antigen Families
- Tysnd1 Deficiency in Mice Interferes with the Peroxisomal Localization of PTS2 Enzymes, Causing Lipid Metabolic Abnormalities and Male Infertility
- A Regulatory Pathway, Ecdysone-Transcription Factor Relish-Cathepsin L, Is Involved in Insect Fat Body Dissociation
- PcG-Mediated Higher-Order Chromatin Structures Modulate Replication Programs at the BX-C
- MSH3 Polymorphisms and Protein Levels Affect CAG Repeat Instability in Huntington's Disease Mice
- JNK-Interacting Protein 3 Mediates the Retrograde Transport of Activated c-Jun N-Terminal Kinase and Lysosomes
- Discovery of a Splicing Regulator Required for Cell Cycle Progression
- Rearrangements of 2.5 Kilobases of Noncoding DNA from the Locus Define Predictive Rules of Genomic -Regulatory Logic
- Admixture Mapping in Lupus Identifies Multiple Functional Variants within IFIH1 Associated with Apoptosis, Inflammation, and Autoantibody Production
- Roles of the Developmental Regulator Homothorax in Limiting Longevity in
- miR-199a-5p Is Upregulated during Fibrogenic Response to Tissue Injury and Mediates TGFbeta-Induced Lung Fibroblast Activation by Targeting Caveolin-1
- A Kinome-Wide RNAi Screen in Glia Reveals That the RIO Kinases Mediate Cell Proliferation and Survival through TORC2-Akt Signaling in Glioblastoma
- Assembly of the Auditory Circuitry by a Genetic Network in the Mouse Brainstem
- SOX2 Co-Occupies Distal Enhancer Elements with Distinct POU Factors in ESCs and NPCs to Specify Cell State
- Retrotransposon Activates Ectopic Expression: A Short Tail
- Confounding by Repetitive Elements and CpG Islands Does Not Explain the Association between Hypomethylation and Genomic Instability
- Cell Reprogramming Requires Silencing of a Core Subset of Polycomb Targets
- Properties and Modeling of GWAS when Complex Disease Risk Is Due to Non-Complementing, Deleterious Mutations in Genes of Large Effect
- Essential Developmental, Genomic Stability, and Tumour Suppressor Functions of the Mouse Orthologue of
- Conditional Inactivation of the DNA Damage Response Gene in Mouse Testis Reveals Separable Roles for Components of the RAD9-RAD1-HUS1 Complex in Meiotic Chromosome Maintenance
- Genome-Wide Analysis Points to Roles for Extracellular Matrix Remodeling, the Visual Cycle, and Neuronal Development in Myopia
- Patterning of Leaf Vein Networks by Convergent Auxin Transport Pathways
- An Evolutionary Perspective on Epistasis and the Missing Heritability
- A Retrotransposon Insertion in the 5′ Regulatory Domain of Ptf1a Results in Ectopic Gene Expression and Multiple Congenital Defects in Danforth's Short Tail Mouse
- The Mub1/Ubr2 Ubiquitin Ligase Complex Regulates the Conserved Dsn1 Kinetochore Protein
- Mutations Can Cause Enamel-Renal Syndrome (ERS)
- Yemanuclein and HIRA Cooperate for Assembly of H3.3-Containing Nucleosomes in the Male Pronucleus
- Hepatocyte Growth Factor, a Determinant of Airspace Homeostasis in the Murine Lung
- ISWI and CHD Chromatin Remodelers Bind Promoters but Act in Gene Bodies
- COM-1 Promotes Homologous Recombination during Meiosis by Antagonizing Ku-Mediated Non-Homologous End Joining
- Control of Multicellular Development by the Physically Interacting Deneddylases DEN1/DenA and COP9 Signalosome
- Antagonism Versus Cooperativity with TALE Cofactors at the Base of the Functional Diversification of Hox Protein Function
- Dynamic Association of NUP98 with the Human Genome
- Ectopic Expression of Induces Spinal Defects, Urogenital Defects, and Anorectal Malformations in Mice
- Regulation of Contributes to the Lineage Potential of Neurogenin3+ Endocrine Precursor Cells in the Pancreas
- Gene-Based Testing of Interactions in Association Studies of Quantitative Traits
- The Amidation Step of Diphthamide Biosynthesis in Yeast Requires , a Gene Identified through Mining the - Interaction Network
- Plant-Symbiotic Fungi as Chemical Engineers: Multi-Genome Analysis of the Clavicipitaceae Reveals Dynamics of Alkaloid Loci
- Genome-Wide Diversity in the Levant Reveals Recent Structuring by Culture
- DNA Methylation Mediated Control of Gene Expression Is Critical for Development of Crown Gall Tumors
- Identification of the SlmA Active Site Responsible for Blocking Bacterial Cytokinetic Ring Assembly over the Chromosome
- Expression of a Novel P22 ORFan Gene Reveals the Phage Carrier State in Typhimurium
- Altered Cohesin Gene Dosage Affects Mammalian Meiotic Chromosome Structure and Behavior
- Quantitative Analysis of Histone Modifications: Formaldehyde Is a Source of Pathological N-Formyllysine That Is Refractory to Histone Deacetylases
- Duplicate Abalone Egg Coat Proteins Bind Sperm Lysin Similarly, but Evolve Oppositely, Consistent with Molecular Mimicry at Fertilization
- Lessons from on the Strengths and Weaknesses of Structured Association Mapping
- DNA–Methylome Analysis of Mouse Intestinal Adenoma Identifies a Tumour-Specific Signature That Is Partly Conserved in Human Colon Cancer
- Transposon Variants and Their Effects on Gene Expression in
- Polygenic Modeling with Bayesian Sparse Linear Mixed Models
- Single Transmembrane Peptide DinQ Modulates Membrane-Dependent Activities
- The JNK Signaling Pathway Activates Expression of Stress Response Genes by Derepressing the Fos/HDAC Repressor Complex
- The Interaction of CtIP and Nbs1 Connects CDK and ATM to Regulate HR–Mediated Double-Strand Break Repair
- Regulation of Metamorphosis by Xenobiotic Response Regulators
- PLOS Genetics
- Archív čísel
- Aktuálne číslo
- Informácie o časopise
Najčítanejšie v tomto čísle- Complex Inheritance of Melanoma and Pigmentation of Coat and Skin in Grey Horses
- Coordination of Chromatid Separation and Spindle Elongation by Antagonistic Activities of Mitotic and S-Phase CDKs
- Autophagy Induction Is a Tor- and Tp53-Independent Cell Survival Response in a Zebrafish Model of Disrupted Ribosome Biogenesis
- Assembly of the Auditory Circuitry by a Genetic Network in the Mouse Brainstem
Prihlásenie#ADS_BOTTOM_SCRIPTS#Zabudnuté hesloZadajte e-mailovú adresu, s ktorou ste vytvárali účet. Budú Vám na ňu zasielané informácie k nastaveniu nového hesla.
- Časopisy