Skip to main content
SpringerLink
Log in

The winged-helix transcription factor JUMU regulates development, nucleolus morphology and function, and chromatin organization of Drosophila melanogaster

  • Published:
Chromosome Research Aims and scope Submit manuscript

Abstract

The PEV-modifying winged-helix/forkhead domain transcription factor JUMU of Drosophila is an essential protein of pleiotropic function. The correct gene dose of jumu is required for nucleolar integrity and correct nucleolus function. Overexpression of jumu results in bloating of euchromatic chromosome arms, displacement of the JUMU protein from the chromocenter and the nucleolus, fragile weak points, and disrupted chromocenter of polytene chromosomes. Overexpression of the acidic C terminus of JUMU alone causes nucleolus disorganization. In addition, euchromatic genes are overexpressed and HP1, which normally accumulates in the pericentric heterochromatin and spreads into euchromatic chromosome arms, although H3-K9 di-methylation remains restricted to the pericentric heterochromatin. The human winged-helix nude gene shows similarities to jumu and its overexpression in Drosophila causes bristle mutations.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9

Similar content being viewed by others

Abbreviations

Domina (Dom):

Synonym of the jumeaux gene

Gal4:

Transcription factor of yeast

HP1:

Heterochromatin protein 1

hsp:

Heatshock promoter

JUMU:

Protein encoded by jumeaux (jumu)

PEV:

Position–effect variegation

E(var):

Enhancer of position–effect variegation

Su(var):

Suppressor of position–effect variegation

UAS:

upstream activating sequence

whn/fkh:

Winged-helix nude/forkhead DNA binding domain

References

  • Andersen JS, Lyon CE, Fox AH, Leung AKL, Lam YW, Steeen H, Mann M, Lamond AI (2002) Directed proteomic analysis of the human nucleolus. Current Biol 12:1–11

    Article  Google Scholar 

  • Bellen HJ, O’Kane CJ, Wilson C, Grossniklaus U, Pearson RK, Gehring WJ (1989) P-element-mediated enhancer detection: a versatile method to study development in Drosophila. Genes Dev 3:1288–1300

    Article  PubMed  CAS  Google Scholar 

  • Blanchard D, Hutter H, Fleenor J, Fire A (2006) A differential cytolocalization assay for analysis of macromolecular assemblies in the eukaryotic cytoplasm. Mol Cell Proteomics 5:2175–2184

    Article  PubMed  CAS  Google Scholar 

  • Brand AH, Perrimon N (1993) Targeted gene expression as a mean of altering cell fates and generating dominant phenotypes. Development 118:401–415

    PubMed  CAS  Google Scholar 

  • Cheah PY, Chia W, Yang X (2000) Jumeaux, a novel Drosophila winged-helix family protein, is required for generating asymmetric neuronal fates. Development 127:3325–3335

    PubMed  CAS  Google Scholar 

  • Chris B, Phelps CB, Brand AH (1998) Ectopic gene expression in Drosophila using GAL4 system. METHODS: A Companion to Methods in Enzymology 14:367–379

    Article  Google Scholar 

  • Cléard F, Delattre M, Spierer P (1997) SU(VAR)3-7, a Drosophila heterochromatin-associated protein and companion of HP1 in the genomic silencing of position-effect variegation. EMBO J 16:5280–5288

    Article  PubMed  Google Scholar 

  • Ebert A, Schotta G, Lein S, Kubicek S, Krauss V, Jenuwein T, Reuter G (2004) Su(var) genes regulate the balance between euchromatin and heterochromatin in Drosophila. Genes Dev 18:2973–2983

    Article  PubMed  CAS  Google Scholar 

  • Ebert A, Lein S, Schotta G, Reuter G (2006) Histone modification and the control of heterochromatic gene silencing in Drosophila. Chromosome Res 14:377–392

    Article  PubMed  CAS  Google Scholar 

  • Eissenberg JC, Hartnett T (1993) A heat-shock-activated cDNA rescues the recessive lethality of mutations in the heterochromatin-associated protein HP1 of Drosophila melanogaster. Mol Gen Genet 240:333–338

    PubMed  CAS  Google Scholar 

  • Eissenberg JC, Elgin SCR (2000) The HP1 protein family: getting a grip on chromatin. Current Opinion Genet Dev 10:204–210

    Article  CAS  Google Scholar 

  • Fischle W (2008) Talk is cheap-cross-talk in establishment, maintenance, and readout of chromatin modifications. Genes Dev 22:3375–3382

    Article  PubMed  CAS  Google Scholar 

  • Frasch M (1991) The maternally expressed Drosophila gene encoding the chromatin-binding protein BJ1 is a homolog of the vertebrate gene regulator of chromatin condensation, RCC1. EMBO J 10:1225–1236

    PubMed  CAS  Google Scholar 

  • Frasch M, Glover DM, Saumweber H (1986) Nuclear antigens follow different pathways into daughter nuclei during mitosis in early Drosophila embryos. J Cell Sci 82:155–172

    PubMed  CAS  Google Scholar 

  • Giot L, Bader JS, Brouwer C et al (2003) A protein interaction map of Drosophila melanogaster. Science 302:1727–1736

    Article  PubMed  CAS  Google Scholar 

  • Greil F, de Wit E, Bussemaker HJ, van Steensel B (2007) HP1 controls genomic targeting of four novel heterochromatin proteins in Drosophila. EMBO J 26:741–751

    Article  PubMed  CAS  Google Scholar 

  • Hari KL, Cook KR, Karpen GH (2001) The Drosophila Su(var)2-10 locus regulates chromosome structure and function and encodes a member of the PIAS protein family. Genes Dev 15:1334–1348

    Article  PubMed  CAS  Google Scholar 

  • Henikoff S (1996) Dosage-dependent modification of position-effect vatiegation in Drosophila. BioEssays 18:401–409

    Article  PubMed  CAS  Google Scholar 

  • Hofmann A, Keinhorst A, Krumm A, Korge G (1987) Regulatory sequences of the Sgs-4 gene of Drosophila melanogaster analysed by P element-mediated transformation. Chromosoma 96:8–17

    Article  PubMed  CAS  Google Scholar 

  • Hofmann A, Brünner M, Korge G (2009) The winged-helix transcription factor JUMU is a haplo suppressor/triplo enhancer of PEV in various tissues but exhibits reverse PEV effects in the brain of Drosophila melanogaster. Chromosome Res 17:347–358

    Article  PubMed  CAS  Google Scholar 

  • Hwang K-K, Eissenberg JC, Worman HJ (2001) Transcriptional repression of euchromatic genes by Drosophila heterochromatin protein 1 and histone modifiers. Proc Natl Acad Sci U S A 98:11423–11427

    Article  PubMed  CAS  Google Scholar 

  • Jaquet Y, Delattre M, Spierer A, Spierer P (2002) Functional dissection of the Drosophila modifier of variegation Su(var)3-7. Development 129:3975–3982

    PubMed  CAS  Google Scholar 

  • James TC, Eissenberg JC, Craig C, Dietrich V, Hobson A, Elgin SC (1989) Distribution patterns of HP1, a heterochromatin-associated nonhistone chromosomal protein of Drosophila. Europ J Cell Biol 50:170–180

    PubMed  CAS  Google Scholar 

  • Jenuwein T, Allis CD (2001) Translating the histone code. Science 293:1074–1080

    Article  PubMed  CAS  Google Scholar 

  • Joppich C, Scholz S, Korge G, Schwendemann A (2009) Umbrea, a chromo shadow domain protein in Drosophila melanogaster heterochromatin, interacts with Hip, HP1 and HOAP. Chromosome Res 17:19–36

    Article  PubMed  CAS  Google Scholar 

  • Karpen GH, Schaefer JE, Laird CD (1988) A drosophila rRNA gene located in euchromatin is active in transcription and nucleolus formation. Genes Development 2:1745–1763

    Article  PubMed  CAS  Google Scholar 

  • Kaufmann E, Knöchel W (1996) Five years on the wings of fork head. Mech Dev 57:3–20

    Article  PubMed  CAS  Google Scholar 

  • Lehmann M, Korge G (1996) The fork head product directly specifies the tissue-specific hormone responsiveness of the Drosophila Sgs4 gene. EMBO J 15:4825–4834

    PubMed  CAS  Google Scholar 

  • Lindsley DT, Zimm GG (1992) The genome of Drosophila melanogaster. Academic, San Diego

    Google Scholar 

  • Li B, Carey M, Workman JL (2007) The role of chromatin during transcription. Cell 128:707–719

    Article  PubMed  CAS  Google Scholar 

  • Liu Y, Lehmann M (2008) A genomic response to the yeast transcription factor GAL4 in Drosophila. Fly 2(2):92–98

    PubMed  Google Scholar 

  • Nehls N, Pfeifer D, Schorpp M, Hedrich H, Boehm T (1994) New member of the winged-helix protein family disrupted in mouse and rat nude mutations. Nature 372:103–107

    Article  PubMed  CAS  Google Scholar 

  • Nishimoto T, Eilen E, Basilico C (1978) Premature of chromosome condensation in a ts DNA-mutant of BHK cells. Cell 15:475–483

    Article  PubMed  CAS  Google Scholar 

  • Patel NH (1994) Imaging neuronal subsets and other cell types in whole-mount Drosophila embryos and larvae using antibody probes. In: Goldstein LSB, Fyrberg EA (eds) Methods in cell biology, vol 44. Academic, Oxford, pp 445–487

    Google Scholar 

  • Peng JC, Karpen GH (2007) H3K9 methylation and RNA interference regulate nucleolar organization and repeated DNA stability. Nat Cell Biol 9:25–35

    Article  PubMed  CAS  Google Scholar 

  • Perrin L, Demakova O, Fanti L, Kallenbach S, Saingery S, Mal’ceva NI, Pimpinelli S, Zhimulev I, Pradel J (1998) Dynamics of the sub-nuclear distribution of Modulo and the regulation of position-effect variegation by nucleolus in Drosophila. J Cell Science 111:2753–2761

    PubMed  CAS  Google Scholar 

  • Perrin L, Romby P, Laurenti P, Bérenger H, Kallenbach S, Bourbon HM, Pradel J (1999) The Drosophila modifier of variegation modulo gene products binds specific RNA sequences at the nucleolus and interacts with DNA and chromatin in a phosphorylation-dependent manner. J Biol Chemistry 274:6315–6323

    Article  CAS  Google Scholar 

  • Reuter G, Spierer P (1992) Position effect variegation and chromatin proteins. BioEssays 14:605–612

    Article  PubMed  CAS  Google Scholar 

  • Reuter G, Dorn R, Wustmann G, Friede B, Rauh G (1986) Third chromosome suppressor of position-effect variegation loci in Drosophila melanogaster. Molec Gen Genet 202(3):481–487

    Article  CAS  Google Scholar 

  • Saeboe-Larssen S, Lyamouri M, Merriam J, Oksvold MP, Lambertsson A (1998) Ribosomal protein insufficiency and the Minute Syndrome in Drosophila: a dose–response relationship. Genetics 148:1215–1224

    PubMed  CAS  Google Scholar 

  • Sambrook J, Fritsch EF, Maniatis T (1998) Molecular cloning: a laboratory manual. Cold Spring Harbor Laboratory, Cold Spring Harbor

    Google Scholar 

  • Schlake T, Schorpp M, Nehls M, Boehm T (1997) The nude gene encodes a sequence-specific DNA binding protein with homologs in organisms that lack an anticipatory immune system. Proc Natl Acad Sci U S A 94:3842–3847

    Article  PubMed  CAS  Google Scholar 

  • Schlake T, Schorpp M, Maul-Pavicic A, Malashenko AM, Boehm T (2000) Forkhead/Winged-Helix transcription factor Whn regulates hair keratine gene expression: molecular analysis of the nude skin phenotype. Dev Dynamics 217:368–376

    Article  CAS  Google Scholar 

  • Schorpp M, Leicht M, Nold E, Hammerschmidt M, Haas-Assenbaum A, Wiest W, Boehm T (2002) A zebrafish orthologue (whnb) of the mouse nude gene is expressed in the epithelial compartment of the embryonic thymic rudiment. Mech Dev 118:179–185

    Article  PubMed  CAS  Google Scholar 

  • Schotta G, Ebert A, Krauss V, Fischer A, Hoffmann J, Rea S, Jenuwein T, Dorn R, Reuter G (2002) Central role of Drosophila SU(VAR)3-9 in histone H3-K9 methylation and heterochromatic gene silencing. EMBO J 21:1121–1131

    Article  PubMed  CAS  Google Scholar 

  • Schüddekopf K, Schorpp M, Boehm T (1996) The whn transcription factor encoded by the nude locus contains an evolutionarily conserved and functionally indispensable activation domain. Proc Natl Acad Sci U S A 93:9661–9664

    Article  PubMed  Google Scholar 

  • Schwendemann A, Matkovic T, Linke C, Klebes A, Hofmann A, Korge G (2008) Hip, an HP1-interacting protein, is a haplo- and triplo-suppressor of position effect variegation. Proc Natl Acad Sci U S A 105:2004–2009

    Article  Google Scholar 

  • Shi W-Y, Skeath JB (2004) The Drosophila RCC1 homolog, Bj1, regulates nucleocytoplasmic transport and neural differentiation during Drosophila development. Dev Biol 270:106–121

    Article  PubMed  CAS  Google Scholar 

  • Shilatifard A (2006) Chromatin modifications by methylation and ubiquitination: implications in the regulation of gene expression. Annu Rev Biochem 75:243–269

    Article  PubMed  CAS  Google Scholar 

  • Spierer A, Seum C, Delattre M, Spierer P (2005) Loss of the modifiers of variegation Su(var)3-7 or HP1 impacts male X polytene chromosome morphology and dosage compensation. J Cell Science 118:5047–5057

    Article  PubMed  CAS  Google Scholar 

  • Spierer A, Begeot F, Spierer P, Delattre M (2008) SU(VAR)3-7 links heterochromatin and dosage compensation in Drosophila. PloS Genetics 4(5):e1000066. doi:10.1371/journal.pgen.1000066

    Article  PubMed  CAS  Google Scholar 

  • Stroedicke M, Karberg S, Korge G (2000) Domina (Dom), a new Drosophila member of the FKH/WH gene family, affects morphogenesis and is a suppressor of position-effect variegation. Mech Dev 96:67–78

    Article  Google Scholar 

  • Sugimura I, Adachi-Yamada T, Nishi Y, Nishida Y (2000) A Drosophila winged-helix nude (WHN)-like transcription factor with essential functions throughout development. Develop Growth Differ 42:237–248

    Article  CAS  Google Scholar 

  • Takiya S, Gazi M, Mach V (2003) The DNA binding of insect Fork head factors is strongly influenced by the negative cooperation of neighbouring bases. Insect Biochem Mol Biol 33:1145–1154

    Article  PubMed  CAS  Google Scholar 

  • Wilson C, Pearson PK, Bellen HJ et al (1989) P-element-mediated enhancer detection: an efficient method for isolating and characterizing developmentally regulated genes in Drosophila. Genes Dev 3:1301–1313

    Article  PubMed  CAS  Google Scholar 

  • Wustmann G, Szidonya J, Taubert H, Reuter G (1989) The genetics of position-effect variegation modifying loci in Drosophila melanogaster. Mol Gen Genet 217:520–527

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We thank E.K.F. Bautz, T. Boehm, S.C.R. Elgin, R.J. Hill, J. Pradel, and G. Reuter for providing us with the antibodies listed in the Supplementary Table 1. We thank U.A. Nuber, Lund, for helpful advice on DNA interaction screening. This work was financially supported by pilot project grants from the Freie Universität Berlin to G. K.

Author information

Authors and Affiliations

  1. Institut für Biologie-Genetik, Freie Universität Berlin, Takustr. 6, 14195, Berlin, Germany

    Annemarie Hofmann, Madeleine Brünner, Alexander Schwendemann, Sascha Karberg, Ansgar Klebes & Günter Korge

  2. Max-Delbrück-Centrum für Molekulare Medizin, Buch, Berlin, Germany

    Martin Strödicke

  3. Fakultät für Mathematik und Naturwissenschaften I, Institut für Biologie, Humboldt Universität Berlin, 10115, Berlin, Germany

    Ansgar Klebes & Harald Saumweber

Authors
  1. Annemarie Hofmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Madeleine Brünner
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Alexander Schwendemann
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Martin Strödicke
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Sascha Karberg
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ansgar Klebes
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Harald Saumweber
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Günter Korge
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Annemarie Hofmann.

Additional information

Responsible Editor: Irina Solovei.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary Figure 1

Nucleolus disorganization in the jumu-overexpressed line Sgs4:Gal4;UAS:jumu. red Cyc3-labeled Aj1 antibody (nucleolus). green Hoechst-stained DNA. (JPEG 61 kb)

High Resolution (TIFF 25516 kb)

Supplementary Figure 2

Jumu overexpression causes transcriptional activation. Microarray analysis of third instar salivary glands that overexpress a Jumu transgene (Schwendemann et al. 2008) revealed 749 transcripts with an enrichment of at least twofold compared to control salivary glands. In contrast, only 30 transcripts are less abundant in the jumu overexpression glands. (JPEG 48 kb)

High Resolution (TIFF 25516 kb)

Supplementary Figure 3

Overexpression of Bj1 in the jumu-overexpressing Sgs:Gal4;UAS:jumu line. above Whole mount salivary glands, phosphatase anti-Bj1 antibody staining. a jumu-overexpressing line Sgs:Gal4;UAS:jumu. b Control. Both glands treated and mounted together. Below squash preparations of polytene chromosomes. green DNA Hoechst staining. red Cyc3 anti-Bj1 antibody staining. FB fat body. (JPEG 106 kb)

High Resolution (TIFF 14371 kb)

Supplementary Figure 4

Macrochaetae of hsp:Gal4;UAS:hwhn flies are long, pale, deformed, and fragile. a hsp:Gal4;UAS:hwhn male. b wild-type male, wings cut. Arrows cuticular bristles. (JPEG 48 kb)

High Resolution (TIFF 2767 kb)

Supplementary Table 1

Tested antibodies with respect to gain-of-function effects of jumu on the chromatin structure. (DOC 44.5 kb)

Supplementary Table 2

List of up- and down-regulated genes after jumu overexpression. Genes are listed that showed at least a twofold difference in expression ratios comparing jumu overexpressing and control salivary glands (median ratios of two independent microarray experiments; further information is available upon request). The columns provide the gene name or symbol (Name), Flybase identification number (ID), and the median log2-transformed expression ratio (ratio (log2)). Genes with transcripts that were enriched in jumu overexpressing glands are highlighted in yellow and those with enrichment in control glands in blue. jumu, hip, Su(var)2-5, and Bj1 red. (XLS 79.5 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hofmann, A., Brünner, M., Schwendemann, A. et al. The winged-helix transcription factor JUMU regulates development, nucleolus morphology and function, and chromatin organization of Drosophila melanogaster . Chromosome Res 18, 307–324 (2010). https://doi.org/10.1007/s10577-010-9118-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10577-010-9118-y

Keywords

Search

Navigation