The heterochromatin-associated protein HP-1 is an essential protein in Drosophila with dosage-dependent effects on position-effect variegation.

Genetics ◽  
1992 ◽  
Vol 131 (2) ◽  
pp. 345-352 ◽  
Author(s):  
J C Eissenberg ◽  
G D Morris ◽  
G Reuter ◽  
T Hartnett
Keyword(s):  
Germ Line ◽  
Position Effect ◽  
Inducible Promoter ◽  
Specific Protein ◽  
P Element ◽  
Position Effect Variegation ◽  
Chromosomal Protein ◽  
Gene Encoding ◽  
Position Effects ◽  
Effect Variegation

Abstract Chromosome rearrangements which place euchromatic genes adjacent to a heterochromatic breakpoint frequently result in gene repression (position-effect variegation). This repression is thought to reflect the spreading of a heterochromatic structure into neighboring euchromatin. Two allelic dominant suppressors of position-effect variegation were found to contain mutations within the gene encoding the heterochromatin-specific chromosomal protein HP-1. The site of mutation for each allele is given: one converts Lys169 into a nonsense (ochre) codon, while the other is a frameshift after Ser10. In flies heterozygous for one of the mutant alleles (Su(var)2-504), a truncated HP-1 protein was detectable by Western blot analysis. An HP-1 minigene, consisting of HP-1 cDNA under the control of an Hsp70 heat-inducible promoter, was transduced into flies by P element-mediated germ line transformation. Heat-shock driven expression of this minigene results in elevated HP-1 protein level and enhancement of position-effect variegation. Levels of variegating gene expression thus appear to depend upon the level of expression of a heterochromatin-specific protein. The implications of these observations for mechanism of heterochromatic position effects and heterochromatin function are discussed.

pitkinD, a Novel Gain-of-Function Enhancer of Position-Effect Variegation, Affects Chromatin Regulation During Oogenesis and Early Embryogenesis in Drosophila

Genetics ◽  
2001 ◽  
Vol 157 (3) ◽  
pp. 1227-1244 ◽  
Author(s):  
Steffi Kuhfittig ◽  
János Szabad ◽  
Gunnar Schotta ◽  
Jan Hoffmann ◽  
Endre Máthé ◽  
...  
Keyword(s):  
Germ Line ◽  
Position Effect ◽  
Early Embryogenesis ◽  
Position Effect Variegation ◽  
Chromatin Regulation ◽  
Gain Of Function ◽  
Position Effects ◽  
Dominant Female ◽  
Effect Variegation ◽  
Female Germ Line

Abstract The vast majority of the >100 modifier genes of position-effect variegation (PEV) in Drosophila have been identified genetically as haplo-insufficient loci. Here, we describe pitkinDominant (ptnD), a gain-of-function enhancer mutation of PEV. Its exceptionally strong enhancer effect is evident as elevated spreading of heterochromatin-induced gene silencing along euchromatic regions in variegating rearrangements. The ptnD mutation causes ectopic binding of the SU(VAR)3-9 heterochromatin protein at many euchromatic sites and, unlike other modifiers of PEV, it also affects stable position effects. Specifically, it induces silencing of white+ transgenes inserted at a wide variety of euchromatic sites. ptnD is associated with dominant female sterility. +/+ embryos produced by ptnD/+ females mated with wild-type males die at the end of embryogenesis, whereas the ptnD/+ sibling embryos arrest development at cleavage cycle 1-3, due to a combined effect of maternally provided mutant product and an early zygotic lethal effect of ptnD. This is the earliest zygotic effect of a mutation so far reported in Drosophila. Germ-line mosaics show that ptn+ function is required for normal development in the female germ line. These results, together with effects on PEV and white+ transgenes, are consistent with the hypothesis that the ptn gene plays an important role in chromatin regulation during development of the female germ line and in early embryogenesis.

Position-effect variegation in Drosophila depends on dose of the gene encoding the E2F transcriptional activator and cell cycle regulator

Development ◽  
1996 ◽  
Vol 122 (6) ◽  
pp. 1949-1956 ◽  
Author(s):  
C. Seum ◽  
A. Spierer ◽  
D. Pauli ◽  
J. Szidonya ◽  
G. Reuter ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Opposite Effect ◽  
Null Allele ◽  
Position Effect ◽  
Transcriptional Activator ◽  
P Element ◽  
Position Effect Variegation ◽  
Gene Encoding ◽  
Cell Cycle Regulator ◽  
Effect Variegation

A dominant mutation due to the insertion of a P-element at 93E on the third chromosome of Drosophila melanogaster enhances position-effect variegation. The corresponding gene was cloned by transposon tagging and the sequence of the transcript revealed that it corresponds to the gene encoding the transcriptional activator and cell cycle regulator dE2F. The transposon-tagged allele is homozygous viable, and the insertion of the transposon in an intron correlates with a strong reduction in the amount of transcript. A homozygous lethal null allele was found to behave as a strong enhancer when heterozygous. Overexpression of the gene in transgenic flies has the opposite effect of suppressing variegation. A link is established here, and discussed, between the dose of a transcriptional activator, which controls the cell cycle, and epigenetic silencing of chromosomal domains in Drosophila.

scholarly journals The AT-Hook Protein D1 Is Essential for Drosophila melanogaster Development and Is Implicated in Position-Effect Variegation

2002 ◽  
Vol 22 (4) ◽  
pp. 1218-1232 ◽  
Author(s):  
Nathalie Aulner ◽  
Caroline Monod ◽  
Guillaume Mandicourt ◽  
Denis Jullien ◽  
Olivier Cuvier ◽  
...  
Keyword(s):  
Drosophila Melanogaster ◽  
Position Effect ◽  
D1 Protein ◽  
P Element ◽  
Centromeric Heterochromatin ◽  
Position Effect Variegation ◽  
Chromosomal Protein ◽  
Mrna Levels ◽  
Satellite Repeats ◽  
Effect Variegation

ABSTRACT We have analyzed the expression pattern of the D1 gene and the localization of its product, the AT hook-bearing nonhistone chromosomal protein D1, during Drosophila melanogaster development. D1 mRNAs and protein are maternally contributed, and the protein localizes to discrete foci on the chromosomes of early embryos. These foci correspond to 1.672- and 1.688-g/cm3 AT-rich satellite repeats found in the centromeric heterochromatin of the X and Y chromosomes and on chromosomes 3 and 4. D1 mRNA levels subsequently decrease throughout later development, followed by the accumulation of the D1 protein in adult gonads, where two distributions of D1 can be correlated to different states of gene activity. We show that the EP473 mutation, a P-element insertion upstream of D1 coding sequences, affects the expression of the D1 gene and results in an embryonic homozygous lethal phenotype correlated with the depletion of D1 protein during embryogenesis. Remarkably, decreased levels of D1 mRNA and protein in heterozygous flies lead to the suppression of position-effect variegation (PEV) of the white gene in the white-mottled (wm4h ) X-chromosome inversion. Our results identify D1 as a DNA-binding protein of known sequence specificity implicated in PEV. D1 is the primary factor that binds the centromeric 1.688-g/cm3 satellite repeats which are likely involved in white-mottled variegation. We propose that the AT-hook D1 protein nucleates heterochromatin assembly by recruiting specialized transcriptional repressors and/or proteins involved in chromosome condensation.

Enhancer of Polycomb Is a Suppressor of Position-Effect Variegation in Drosophila melanogaster

Genetics ◽  
1998 ◽  
Vol 148 (1) ◽  
pp. 211-220
Author(s):  
Donald A R Sinclair ◽  
Nigel J Clegg ◽  
Jennifer Antonchuk ◽  
Thomas A Milne ◽  
Kryn Stankunas ◽  
...  
Keyword(s):  
Sequence Similarity ◽  
Position Effect ◽  
Polycomb Group ◽  
P Element ◽  
Homeotic Gene ◽  
Position Effect Variegation ◽  
Negative Regulators ◽  
Recombination Mapping ◽  
Effect Variegation ◽  
Homeotic Gene Expression

Abstract Polycomb group (PcG) genes of Drosophila are negative regulators of homeotic gene expression required for maintenance of determination. Sequence similarity between Polycomb and Su(var)205 led to the suggestion that PcG genes and modifiers of position-effect variegation (PEV) might function analogously in the establishment of chromatin structure. If PcG proteins participate directly in the same process that leads to PEV, PcG mutations should suppress PEV. We show that mutations in E(Pc), an unusual member of the PcG, suppress PEV of four variegating rearrangements: In(l)wm4, BSV, T(2;3)SbV, and In(2R)bwVDe2. Using reversion of a P element insertion, deficiency mapping, and recombination mapping as criteria, homeotic effects and suppression of PEV associated with E(Pc) co-map. Asx is an enhancer of PEV, whereas nine other PcG loci do not affect PEV. These results support the conclusion that there are fewer similarities between PcG genes and modifiers of PEV than previously supposed. However, E(Pc) appears to be an important link between the two groups. We discuss why Asx might act as an enhancer of PEV.

scholarly journals Mutation in P0, a Dual Function Ribosomal Protein/Apurinic/Apyrimidinic Endonuclease, Modifies Gene Expression and Position Effect Variegation in Drosophila

Genetics ◽  
1998 ◽  
Vol 150 (4) ◽  
pp. 1487-1495
Author(s):  
Maxim V Frolov ◽  
James A Birchler
Keyword(s):  
Gene Expression ◽  
Ribosomal Protein ◽  
Position Effect ◽  
P Element ◽  
Dual Function ◽  
Insertion Mutant ◽  
Position Effect Variegation ◽  
Element Insertion ◽  
Effect Variegation ◽  
Ribosomal Protein P0

Abstract In a search for modifiers of gene expression with the white eye color gene as a target, a third chromosomal P-element insertion mutant l(3)01544 has been identified that exhibits a strong pigment increase in a white-apricot background. Molecular analysis shows that the P-element insertion is found in the first intron of the gene surrounding the insertion site. Sequencing both the cDNA and genomic fragments revealed that the identified gene is identical to one encoding ribosomal protein P0/apurinic/apyrimidinic endonuclease. The P-element-induced mutation, l(3)01544, affects the steady-state level of white transcripts and transcripts of some other genes. In addition, l(3)01544 suppresses the variegated phenotypes of In(1)wm4h and In(1)y3P, suggesting a potential involvement of the P0 protein in modifying position effect variegation. The revertant generated by the precise excision of the P element has lost all mutant phenotypes. Recent work revealed that Drosophila ribosomal protein P0 contains an apurinic/apyrimidinic endonuclease activity. Our results suggest that this multifunctional protein is also involved in regulation of gene expression in Drosophila.

CORRIGENDA

Genetics ◽  
1996 ◽  
Vol 144 (3) ◽  
pp. 1329B-1329B
Keyword(s):  
Drosophila Melanogaster ◽  
Position Effect ◽  
Position Effect Variegation ◽  
Gene Encoding ◽  
Effect Variegation ◽  
Adenosylmethionine Synthetase

Abstract In the paper by J. Larsson, J. Zhang and A. Rasmuson-Lestander (Genetics  143:  887–896; June, 1996) entitled “Mutations in the Drosophila melanogaster gene encoding S-adenosylmethionine synthetase suppress position-effect variegation,” the word “synthetase” was omitted from the title.

Mechanisms for the construction and developmental control of heterochromatin formation and imprinted chromosome domains

Development ◽  
1990 ◽  
Vol 108 (Supplement) ◽  
pp. 35-45 ◽  
Author(s):  
Kenneth D. Tartof ◽  
Marilyn Bremer
Keyword(s):  
Position Effect ◽  
Model System ◽  
Chromosome Inactivation ◽  
Position Effect Variegation ◽  
Position Effects ◽  
Developmental Control ◽  
Heterochromatin Formation ◽  
Material Basis ◽  
Chromosome Domains ◽  
Effect Variegation

The study of variegating position effects in Drosophila provides a model system to explore the mechanism and material basis for the construction and developmental control of heterochromatin domains and the imprinted genomic structures that they may create. The results of our experiments in this regard have implications for a diverse assortment of long-range chromosome phenomena related to gene and chromosome inactivation. Specifically, as a consequence of our studies on position effect variegation, we propose a simple mechanism of X-chromosome inactivation, suggest a purpose for genomic imprinting, and postulate a general means for regulating the time in development at which certain genes become heterochromatically repressed.

scholarly journals The dose of a putative ubiquitin-specific protease affects position-effect variegation in Drosophila melanogaster.

1996 ◽  
Vol 16 (10) ◽  
pp. 5717-5725 ◽  
Author(s):  
S Henchoz ◽  
F De Rubertis ◽  
D Pauli ◽  
P Spierer
Keyword(s):  
Drosophila Melanogaster ◽  
Position Effect ◽  
Transcript Level ◽  
Open Reading Frame ◽  
P Element ◽  
Position Effect Variegation ◽  
Reading Frame ◽  
Effect Variegation ◽  
Specific Protease ◽  
Ubiquitin Specific Protease

A dominant insertional P-element mutation enhances position-effect variegation in Drosophila melanogaster. The mutation is homozygous, viable, and fertile and maps at 64E on the third chromosome. The corresponding gene was cloned by transposon tagging. Insertion of the transposon upstream of the open reading frame correlates with a strong reduction of transcript level. A transgene was constructed with the cDNA and found to have the effect opposite from that of the mutation, namely, to suppress variegation. Sequencing of the cDNA reveals a large open reading frame encoding a putative ubiquitin-specific protease (Ubp). Ubiquitin marks various proteins, frequently for proteasome-dependent degradation. Ubps can cleave the ubiquitin part from these proteins. We discuss the link established here between a deubiquitinating enzyme and epigenetic silencing processes.

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