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 Su(z)12, a novelDrosophilaPolycomb group gene that is conserved in vertebrates and plants

Development ◽  
2001 ◽  
Vol 128 (17) ◽  
pp. 3371-3379 ◽  
Author(s):  
Anna Birve ◽  
Aditya K. Sengupta ◽  
Dirk Beuchle ◽  
Jan Larsson ◽  
James A. Kennison ◽  
...  
Keyword(s):  
Hox Genes ◽  
Position Effect ◽  
Polycomb Group ◽  
Homeotic Gene ◽  
Homeotic Genes ◽  
Position Effect Variegation ◽  
Regulatory Machinery ◽  
Effect Variegation ◽  
Arabidopsis Proteins ◽  
Homeotic Gene Expression

In both Drosophila and vertebrates, spatially restricted expression of HOX genes is controlled by the Polycomb group (PcG) repressors. Here we characterize a novel Drosophila PcG gene, Suppressor of zeste 12 (Su(z)12). Su(z)12 mutants exhibit very strong homeotic transformations and Su(z)12 function is required throughout development to maintain the repressed state of HOX genes. Unlike most other PcG mutations, Su(z)12 mutations are strong suppressors of position-effect variegation (PEV), suggesting that Su(z)12 also functions in heterochromatin-mediated repression. Furthermore, Su(z)12 function is required for germ cell development. The Su(z)12 protein is highly conserved in vertebrates and is related to the Arabidopsis proteins EMF2, FIS2 and VRN2. Notably, EMF2 is a repressor of floral homeotic genes. These results suggest that at least some of the regulatory machinery that controls homeotic gene expression is conserved between animals and plants.

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.

The Additional sex combs gene of Drosophila encodes a chromatin protein that binds to shared and unique Polycomb group sites on polytene chromosomes

Development ◽  
1998 ◽  
Vol 125 (7) ◽  
pp. 1207-1216 ◽  
Author(s):  
D.A. Sinclair ◽  
T.A. Milne ◽  
J.W. Hodgson ◽  
J. Shellard ◽  
C.A. Salinas ◽  
...  
Keyword(s):  
Target Genes ◽  
Position Effect ◽  
Polytene Chromosomes ◽  
Polycomb Group ◽  
Position Effect Variegation ◽  
Sex Combs ◽  
Effect Variegation ◽  
The Central Nervous System ◽  
Additional Sex Combs ◽  
Site Recognition

The Additional sex combs (Asx) gene of Drosophila is a member of the Polycomb group of genes, which are required for maintenance of stable repression of homeotic and other loci. Asx is unusual among the Polycomb group because: (1) one Asx allele exhibits both anterior and posterior transformations; (2) Asx mutations enhance anterior transformations of trx mutations; (3) Asx mutations exhibit segmentation phenotypes in addition to homeotic phenotypes; (4) Asx is an Enhancer of position-effect variegation and (5) Asx displays tissue-specific derepression of target genes. Asx was cloned by transposon tagging and encodes a protein of 1668 amino acids containing an unusual cysteine cluster at the carboxy terminus. The protein is ubiquitously expressed during development. We show that Asx is required in the central nervous system to regulate Ultrabithorax. ASX binds to multiple sites on polytene chromosomes, 70% of which overlap those of Polycomb, polyhomeotic and Polycomblike, and 30% of which are unique. The differences in target site recognition may account for some of the differences in Asx phenotypes relative to other members of the Polycomb group.

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.

scholarly journals Conservation of brown gene trans-inactivation in Drosophila.

Genetics ◽  
1995 ◽  
Vol 140 (1) ◽  
pp. 193-199
Author(s):  
L E Martin-Morris ◽  
S Henikoff
Keyword(s):  
Sequence Similarity ◽  
Position Effect ◽  
Regulatory Sequences ◽  
Position Effect Variegation ◽  
Protein Coding ◽  
Dominant Position ◽  
Reading Frame ◽  
Functional Homology ◽  
Effect Variegation ◽  
Conceptual Translation

Abstract The mechanism underlying trans-inactivation associated with dominant position effect variegation (PEV) of the Drosophila melanogaster brown gene has been addressed by a comparison with its D. virilis homologue. This comparison revealed: 86% identity between conceptual translation products of the brown gene from these two species, functional homology, as the D. virilis gene rescues a D. melanogaster null brown mutation, and conservation of the sequences required for trans-inactivation, as the D. virilis gene in D. melanogaster is subject to dominant PEV. An extended region of sequence similarity upstream of the open reading frame is observed. As the D. virilis homologue is functionally interchangeable with the D. melanogaster gene, these genes must share regulatory sequences as well as protein coding homology. These results support a model in which trans-inactivation is mediated by a heterochromatin-sensitive transcription factor.

scholarly journals The lawc Gene Is a New Member of the trithorax-Group That Affects the Function of the gypsy Insulator of Drosophila

Genetics ◽  
1999 ◽  
Vol 152 (3) ◽  
pp. 1045-1055
Author(s):  
Izanne D Zorin ◽  
Tatiana I Gerasimova ◽  
Victor G Corces
Keyword(s):  
Gene Transcription ◽  
Imaginal Disc ◽  
Position Effect ◽  
Ectopic Expression ◽  
Higher Order ◽  
Homeotic Gene ◽  
Position Effect Variegation ◽  
Gypsy Insulator ◽  
Trithorax Group ◽  
Effect Variegation

Abstract Mutations in the lawc gene result in a pleiotropic phenotype that includes homeotic transformation of the arista into leg. lawc mutations enhance the phenotype of trx-G mutations and suppress the phenotype of Pc mutations. Mutations in lawc affect homeotic gene transcription, causing ectopic expression of Antennapedia in the eye-antenna imaginal disc. These results suggest that lawc is a new member of the trithorax family. The lawc gene behaves as an enhancer of position-effect variegation and interacts genetically with mod(mdg4), which is a component of the gypsy insulator. In addition, mutations in the lawc gene cause alterations in the punctated distribution of mod(mdg4) protein within the nucleus. These results suggest that the lawc protein is involved in regulating the higher-order organization of chromatin.

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.

scholarly journals Mutations in the Drosophila melanogaster Gene Encoding S-adenosylmethionine Suppress Position-Effect Variegation

Genetics ◽  
1996 ◽  
Vol 143 (2) ◽  
pp. 887-896 ◽  
Author(s):  
Jan Larsson ◽  
Jingpu Zhang ◽  
Åsa Rasmuson-Lestander
Keyword(s):  
Drosophila Melanogaster ◽  
Chromatin Structure ◽  
Position Effect ◽  
Regulatory Region ◽  
Polycomb Group ◽  
Position Effect Variegation ◽  
Gene Encoding ◽  
Sex Combs ◽  
S Alleles ◽  
Effect Variegation

Abstract In Drosophila melanogaster, the study of trans-acting modifier mutations of position-effect variegation and Polycomb group (Pc-G) genes have been useful tools to investigate genes involved in chromatin structure. We have cloned a modifier gene, Suppesssm of zeste 5 (Su(z)5), which encodes Sadenosylmethionine synthetase, and we present here molecular results and data concerning its expression in mutants and genetic interactions. The mutant alleles Su(z)5, l(2)R23 and l(2)M6 show suppression of wm4 and also of two white mutants induced by roo element insertions in the regulatory region i.e., wis (in combination with z  1) and wsp1. Two of the Su(z)S alleles, as well as a deletion of the gene, also act as enhancers of PoZycomb by increasing the size of sex combs on midleg. The results suggest that Su(z)5 is connected with regulation of chromatin structure. The enzyme Sadenosylmethionine synthetase is involved in the synthesis of Sadenosylmethionine, a methyl group donor and also, after decarboxylation, a propylamino group donor in the bio-synthesis of polyamines. Our results from HPLC analysis show that in ovaries from heterozygous Su(z)5 mutants the content of spermine is significantly reduced. Results presented here suggest that polyamines are an important molecule class in the regulation of chromatin structure.

scholarly journals Dosage-dependent modifiers of position effect variegation in Drosophila and a mass action model that explains their effect.

Genetics ◽  
1988 ◽  
Vol 120 (1) ◽  
pp. 181-198
Author(s):  
J Locke ◽  
M A Kotarski ◽  
K D Tartof
Keyword(s):  
Position Effect ◽  
Class Ii ◽  
Mass Action ◽  
P Element ◽  
Class I ◽  
Gene Copy ◽  
Position Effect Variegation ◽  
Mass Action Model ◽  
Effect Variegation ◽  
Action Model

Abstract Twelve dominant enhancers of position effect variegation, representing four loci on the second and third chromosomes of Drosophila melanogaster, have been induced by P-element mutagenesis. Instead of simple transposon insertions, seven of these mutations are cytologically visible duplications and three are deficiencies. The duplications define two distinct regions, each coinciding with a locus that also behaves as a dominant haplo-dependent suppressor of variegation. Conversely, two of the deficiencies overlap with a region that contains a haplo-dependent enhancer of variegation while duplications of this same region act to suppress variegation. The third deficiency defines another haplo-dependent enhancer. These data indicate that loci capable of modifying variegation do so in an antipodal fashion through changes in the wild-type gene copy number and may be divided into two reciprocally acting classes. Class I modifiers enhance variegation when duplicated or suppress variegation when deficient. Class II modifiers enhance when deficient but suppress when duplicated. From our data, and those of others, we propose that in Drosophila there are about 20 to 30 dominant loci that modify variegation. Most appear to be of the class I type whereas only two class II modifiers have been identified so far. From these observations we put forth a model, based on the law of mass action, for understanding how such suppressor-enhancer loci function. We propose that each class I modifier codes for a structural protein component of heterochromatin and their effects on variegation are a consequence of their dosage dependent influence on the extent of the assembly of heterochromatin at the chromosomal site of the position effect. It is further proposed that class II modifiers may inhibit the class I products directly, bind to hypothetical termination sites that define heterochromatin boundaries or promote euchromatin formation. Consistent with our mass action model we find that combining two enhancers together produce additive and not epistatic effects. Also, since different enhancers have different relative strengths on different variegating mutants, we suggest that heterochromatic domains are constructed by a combinatorial association of proteins. The mass action model proposed here is of general significance for any assembly driven reaction and has implications for understanding a wide variety of biological phenomena.(ABSTRACT TRUNCATED AT 400 WORDS)

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