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 ◽  
...  

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.

Genetics ◽  
1998 ◽  
Vol 148 (1) ◽  
pp. 211-220
Author(s):  
Donald A R Sinclair ◽  
Nigel J Clegg ◽  
Jennifer Antonchuk ◽  
Thomas A Milne ◽  
Kryn Stankunas ◽  
...  

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.


Development ◽  
1998 ◽  
Vol 125 (18) ◽  
pp. 3543-3551 ◽  
Author(s):  
S. Bel ◽  
N. Core ◽  
M. Djabali ◽  
K. Kieboom ◽  
N. Van der Lugt ◽  
...  

In Drosophila and mouse, Polycomb group genes are involved in the maintenance of homeotic gene expression patterns throughout development. Here we report the skeletal phenotypes of compound mutants for two Polycomb group genes bmi1 and M33. We show that mice deficient for both bmi1 and M33 present stronger homeotic transformations of the axial skeleton as compared to each single Polycomb group mutant, indicating strong dosage interactions between those two genes. These skeletal transformations are accompanied with an enhanced shift of the anterior limit of expression of several Hox genes in the somitic mesoderm. Our results demonstrate that in mice the Polycomb group genes act in synergy to control the nested expression pattern of some Hox genes in somitic mesodermal tissues during development.


Development ◽  
1998 ◽  
Vol 125 (7) ◽  
pp. 1207-1216 ◽  
Author(s):  
D.A. Sinclair ◽  
T.A. Milne ◽  
J.W. Hodgson ◽  
J. Shellard ◽  
C.A. Salinas ◽  
...  

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.


Development ◽  
1994 ◽  
Vol 120 (9) ◽  
pp. 2629-2636 ◽  
Author(s):  
A. Lonie ◽  
R. D'Andrea ◽  
R. Paro ◽  
R. Saint

The Polycomblike gene of Drosophila melanogaster, a member of the Polycomb Group of genes, is required for the correct spatial expression of the homeotic genes of the Antennapaedia and Bithorax Complexes. Mutations in Polycomb Group genes result in ectopic homeotic gene expression, indicating that Polycomb Group proteins maintain the transcriptional repression of specific homeotic genes in specific tissues during development. We report here the isolation and molecular characterisation of the Polycomblike gene. The Polycomblike transcript encodes an 857 amino acid protein with no significant homology to other proteins. Antibodies raised against the product of this open reading frame were used to show that the Polycomblike protein is found in all nuclei during embryonic development. Antibody staining also revealed that the Polycomblike protein is found on larval salivary gland polytene chromosomes at about 100 specific loci, the same loci to which the Polycomb and polyhomeotic proteins, two other Polycomb Group proteins, are found. These data add further support for a model in which Polycomb Group proteins form multimeric protein complexes at specific chromosomal loci to repress transcription at those loci.


Genetics ◽  
1999 ◽  
Vol 152 (3) ◽  
pp. 1045-1055
Author(s):  
Izanne D Zorin ◽  
Tatiana I Gerasimova ◽  
Victor G Corces

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.


Genetics ◽  
1996 ◽  
Vol 143 (2) ◽  
pp. 887-896 ◽  
Author(s):  
Jan Larsson ◽  
Jingpu Zhang ◽  
Åsa Rasmuson-Lestander

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.


Development ◽  
1998 ◽  
Vol 125 (20) ◽  
pp. 4055-4066 ◽  
Author(s):  
K. Stankunas ◽  
J. Berger ◽  
C. Ruse ◽  
D.A. Sinclair ◽  
F. Randazzo ◽  
...  

The Polycomb group of genes in Drosophila are homeotic switch gene regulators that maintain homeotic gene repression through a possible chromatin regulatory mechanism. The Enhancer of Polycomb (E(Pc)) gene of Drosophila is an unusual member of the Polycomb group. Most PcG genes have homeotic phenotypes and are required for repression of homeotic loci, but mutations in E(Pc) exhibit no homeotic transformations and have only a very weak effect on expression of Abd-B. However, mutations in E(Pc) are strong enhancers of mutations in many Polycomb group genes and are also strong suppressors of position-effect variegation, suggesting that E(Pc) may have a wider role in chromatin formation or gene regulation than other Polycomb group genes. E(Pc) was cloned by transposon tagging, and encodes a novel 2023 amino acid protein with regions enriched in glutamine, alanine and asparagine. E(Pc) is expressed ubiquitously in Drosophila embryogenesis. E(Pc) is a chromatin protein, binding to polytene chromosomes at about 100 sites, including the Antennapedia but not the Bithorax complex, 29% of which are shared with Polycomb-binding sites. Surprisingly, E(Pc) was not detected in the heterochromatic chromocenter. This result suggests that E(Pc) has a functional rather than structural role in heterochromatin formation and argues against the heterochromatin model for PcG function. Using homology cloning techniques, we identified a mouse homologue of E(Pc), termed Epc1, a yeast protein that we name EPL1, and as well as additional ESTs from Caenorhabditis elegans, mice and humans. Epc1 shares a long, highly conserved domain in its amino terminus with E(Pc) that is also conserved in yeast, C. elegans and humans. The occurrence of E(Pc) across such divergent species is unusual for both PcG proteins and for suppressors of position-effect variegation, and suggests that E(Pc) has an important role in the regulation of chromatin structure in eukaryotes.


Genetics ◽  
2000 ◽  
Vol 154 (2) ◽  
pp. 657-668 ◽  
Author(s):  
Randy Mottus ◽  
Richard E Sobel ◽  
Thomas A Grigliatti

Abstract For many years it has been noted that there is a correlation between acetylation of histones and an increase in transcriptional activity. One prediction, based on this correlation, is that hypomorphic or null mutations in histone deacetylase genes should lead to increased levels of histone acetylation and result in increased levels of transcription. It was therefore surprising when it was reported, in both yeast and fruit flies, that mutations that reduced or eliminated a histone deacetylase resulted in transcriptional silencing of genes subject to telomeric and heterochromatic position effect variegation (PEV). Here we report the first mutational analysis of a histone deacetylase in a multicellular eukaryote by examining six new mutations in HDAC1 of Drosophila melanogaster. We observed a suite of phenotypes accompanying the mutations consistent with the notion that HDAC1 acts as a global transcriptional regulator. However, in contrast to recent findings, here we report that specific missense mutations in the structural gene of HDAC1 suppress the silencing of genes subject to PEV. We propose that the missense mutations reported here are acting as antimorphic mutations that “poison” the deacetylase complex and propose a model that accounts for the various phenotypes associated with lesions in the deacetylase locus.


Genetics ◽  
1998 ◽  
Vol 149 (1) ◽  
pp. 257-275 ◽  
Author(s):  
Sophie Netter ◽  
Marie-Odile Fauvarque ◽  
Ruth Diez del Corral ◽  
Jean-Maurice Dura ◽  
Dario Coen

AbstractWe used the white gene as an enhancer trap and reporter of chromatin structure. We collected white+ transgene insertions presenting a peculiar pigmentation pattern in the eye: white expression is restricted to the dorsal half of the eye, with a clear-cut dorsal/ventral (D/V) border. This D/V pattern is stable and heritable, indicating that phenotypic expression of the white reporter reflects positional information in the developing eye. Localization of these transgenes led us to identify a unique genomic region encompassing 140 kb in 69D1–3 subject to this D/V effect. This region contains at least three closely related homeobox-containing genes that are constituents of the iroquois complex (IRO-C). IRO-C genes are coordinately regulated and implicated in similar developmental processes. Expression of these genes in the eye is regulated by the products of the Polycomb -group (Pc-G) and trithorax-group (trx-G) genes but is not modified by classical modifiers of position-effect variegation. Our results, together with the report of a Pc -G binding site in 69D, suggest that we have identified a novel cluster of target genes for the Pc-G and trx-G products. We thus propose that ventral silencing of the whole IRO-C in the eye occurs at the level of chromatin structure in a manner similar to that of the homeotic gene complexes, perhaps by local compaction of the region into a heterochromatin-like structure involving the Pc-G products.


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