The domino gene of Drosophila encodes novel members of the SWI2/SNF2 family of DNA-dependent ATPases, which contribute to the silencing of homeotic genes

Development ◽  
2001 ◽  
Vol 128 (8) ◽  
pp. 1429-1441 ◽  
Author(s):  
M.L. Ruhf ◽  
A. Braun ◽  
O. Papoulas ◽  
J.W. Tamkun ◽  
N. Randsholt ◽  
...  
Keyword(s):  
Polytene Chromosomes ◽  
Gene Mutations ◽  
Polycomb Group ◽  
Protein Isoforms ◽  
Homeotic Genes ◽  
Loss Of Function ◽  
Trithorax Group ◽  
A Subunit ◽  
The Common ◽  
Hematopoietic Disorders

The Drosophila domino gene has been isolated in a screen for mutations that cause hematopoietic disorders. Generation and analysis of loss-of-function domino alleles show that the phenotypes are typical for proliferation gene mutations. Clonal analysis demonstrates that domino is necessary for cell viability and proliferation, as well as for oogenesis. domino encodes two protein isoforms of 3202 and 2498 amino acids, which contain a common N-terminal region but divergent C termini. The common region includes a 500 amino acid DNA-dependent ATPase domain of the SWI2/SNF2 family of proteins, which function via interaction with chromatin. We show that, although domino alleles do not exhibit homeotic phenotypes by themselves, domino mutations enhance Polycomb group mutations and counteract Trithorax group effects. The Domino proteins are present in large complexes in embryo extracts, and one isoform binds to a number of discrete sites on larval polytene chromosomes. Altogether, the data lead us to propose that domino acts as a repressor by interfering with chromatin structure. This activity is likely to be performed as a subunit of a chromatin-remodeling complex.

scholarly journals TheTrithorax-mimicAllele ofEnhancer of zesteRenders Active Domains of Target Genes Accessible toPolycomb-Group-Dependent Silencing inDrosophila melanogaster

Genetics ◽  
2001 ◽  
Vol 159 (3) ◽  
pp. 1135-1150 ◽  
Author(s):  
Izabella Bajusz ◽  
László Sipos ◽  
Zoltán Györgypál ◽  
Elizabeth A Carrington ◽  
Richard S Jones ◽  
...  
Keyword(s):  
Transcriptional Repression ◽  
Target Genes ◽  
Critical Role ◽  
Polycomb Group ◽  
Single Amino Acid ◽  
Homeotic Genes ◽  
Loss Of Function ◽  
Chromatin Domains ◽  
Trithorax Group ◽  
Inactive Chromatin

AbstractTwo antagonistic groups of genes, the trithorax- and the Polycomb-group, are proposed to maintain the appropriate active or inactive state of homeotic genes set up earlier by transiently expressed segmentation genes. Although some details about the mechanism of maintenance are available, it is still unclear how the initially active or inactive chromatin domains are recognized by either the trithorax-group or the Polycomb-group proteins. We describe an unusual dominant allele of a Polycomb-group gene, Enhancer of zeste, which mimics the phenotype of loss-of-function mutations in trithorax-group genes. This mutation, named E(z)Trithorax mimic [E(z)Trm], contains a single-amino-acid substitution in the conserved SET domain. The strong dominant trithorax-like phenotypes elicited by this E(z) allele suggest that the mutated arginine-741 plays a critical role in distinguishing between active and inactive chromatin domains of the homeotic gene complexes. We have examined the modification of E(z)Trm phenotypes by mutant alleles of PcG and trxG genes and other mutations that alter the phosphorylation of nuclear proteins, covalent modifications of histones, or histone dosage. These data implicate some trxG genes in transcriptional repression as well as activation and provide genetic evidence for involvement of histone modifications in PcG/trxG-dependent transcriptional regulation.

scholarly journals DSP1, an HMG-like Protein, Is Involved in the Regulation of Homeotic Genes

Genetics ◽  
2001 ◽  
Vol 157 (1) ◽  
pp. 237-244
Author(s):  
M Decoville ◽  
E Giacomello ◽  
M Leng ◽  
D Locker
Keyword(s):  
Null Allele ◽  
Genetic Interaction ◽  
Polycomb Group ◽  
Homeotic Genes ◽  
Loss Of Function ◽  
Sex Combs Reduced ◽  
Trithorax Group ◽  
Sex Combs ◽  
Normal Expression ◽  
Sex Comb

Abstract The Drosophila dsp1 gene, which encodes an HMG-like protein, was originally identified in a screen for corepressors of Dorsal. Here we report that loss of dsp1 function causes homeotic transformations resembling those associated with loss of function in the homeotic genes Sex combs reduced (Scr), Ultrabithorax (Ubx), and Abdominal-B. The expression pattern of Scr is altered in dsp1 mutant imaginal discs, indicating that dsp1 is required for normal expression of this gene. Genetic interaction studies reveal that a null allele of dsp1 enhances trithorax-group gene (trx-G) mutations and partially suppresses Polycomb-group gene (Pc-G) mutations. On the contrary, overexpression of dsp1 induces an enhancement of the transformation of wings into halteres and of the extra sex comb phenotype of Pc. In addition, dsp1 male mutants exhibit a mild transformation of A4 into A5. Comparison of the chromatin structure at the Mcp locus in wild-type and dsp1 mutant embryos reveals that the 300-bp DNase I hypersensitive region is absent in a dsp1 mutant context. We propose that DSP1 protein is a chromatin remodeling factor, acting as a trx-G or a Pc-G protein depending on the considered function.

The Drosophila kismet gene is related to chromatin-remodeling factors and is required for both segmentation and segment identity

Development ◽  
1999 ◽  
Vol 126 (6) ◽  
pp. 1175-1187 ◽  
Author(s):  
G. Daubresse ◽  
R. Deuring ◽  
L. Moore ◽  
O. Papoulas ◽  
I. Zakrajsek ◽  
...  
Keyword(s):  
Chromatin Remodeling ◽  
Homeotic Genes ◽  
Loss Of Function ◽  
Larval Body ◽  
Sex Combs Reduced ◽  
Trithorax Group ◽  
Sex Combs ◽  
Pair Rule Gene ◽  
Body Segmentation ◽  
Group Protein

The Drosophila kismet gene was identified in a screen for dominant suppressors of Polycomb, a repressor of homeotic genes. Here we show that kismet mutations suppress the Polycomb mutant phenotype by blocking the ectopic transcription of homeotic genes. Loss of zygotic kismet function causes homeotic transformations similar to those associated with loss-of-function mutations in the homeotic genes Sex combs reduced and Abdominal-B. kismet is also required for proper larval body segmentation. Loss of maternal kismet function causes segmentation defects similar to those caused by mutations in the pair-rule gene even-skipped. The kismet gene encodes several large nuclear proteins that are ubiquitously expressed along the anterior-posterior axis. The Kismet proteins contain a domain conserved in the trithorax group protein Brahma and related chromatin-remodeling factors, providing further evidence that alterations in chromatin structure are required to maintain the spatially restricted patterns of homeotic gene transcription.

Altered cellular proliferation and mesoderm patterning in Polycomb-M33-deficient mice

Development ◽  
1997 ◽  
Vol 124 (3) ◽  
pp. 721-729 ◽  
Author(s):  
N. Core ◽  
S. Bel ◽  
S.J. Gaunt ◽  
M. Aurrand-Lions ◽  
J. Pearce ◽  
...  
Keyword(s):  
Cellular Proliferation ◽  
Hox Genes ◽  
Es Cells ◽  
Embryonic Stem ◽  
Axial Skeleton ◽  
Polycomb Group ◽  
Homeotic Genes ◽  
Loss Of Function ◽  
Polycomb Group Genes

In Drosophila, the trithorax-group and the Polycomb-group genes are necessary to maintain the expression of the homeobox genes in the appropriate segments. Loss-of-function mutations in those groups of genes lead to misexpression of the homeotic genes resulting in segmental homeotic transformations. Recently, mouse homologues of the Polycomb-group genes were identified including M33, the murine counterpart of Polycomb. In this report, M33 was targeted in mice by homologous recombination in embryonic stem (ES) cells to assess its function during development. Homozygous M33 (−/−) mice show greatly retarded growth, homeotic transformations of the axial skeleton, sternal and limb malformations and a failure to expand in vitro of several cell types including lymphocytes and fibroblasts. In addition, M33 null mutant mice show an aggravation of the skeletal malformations when treated to RA at embryonic day 7.5, leading to the hypothesis that, during development, the M33 gene might play a role in defining access to retinoic acid response elements localised in the regulatory regions of several Hox genes.

scholarly journals The Drosophila snr1 and brm proteins are related to yeast SWI/SNF proteins and are components of a large protein complex.

1995 ◽  
Vol 6 (7) ◽  
pp. 777-791 ◽  
Author(s):  
A K Dingwall ◽  
S J Beek ◽  
C M McCallum ◽  
J W Tamkun ◽  
G V Kalpana ◽  
...  
Keyword(s):  
Gene Transcription ◽  
Protein Complex ◽  
Molecular Mechanisms ◽  
Protein A ◽  
Polycomb Group ◽  
Homeotic Gene ◽  
Spatial And Temporal Patterns ◽  
Trithorax Group ◽  
Activator Proteins ◽  
A Subunit

During most of Drosophila development the regulation of homeotic gene transcription is controlled by two groups of regulatory genes, the trithorax group of activators and the Polycomb group of repressors. brahma (brm), a member of the trithorax group, encodes a protein related to the yeast SWI2/SNF2 protein, a subunit of a protein complex that assists sequence-specific activator proteins by alleviating the repressive effects of chromatin. To learn more about the molecular mechanisms underlying the regulation of homeotic gene transcription, we have investigated whether a similar complex exists in flies. We identified the Drosophila snr1 gene, a potential homologue of the yeast SNF5 gene that encodes a subunit of the yeast SWI/SNF complex. The snr1 gene is essential and genetically interacts with brm and trithorax (trx), suggesting cooperation in regulating homeotic gene transcription. The spatial and temporal patterns of expression of snr1 are similar to those of brm. The snr1 and brm proteins are present in a large (> 2 x 10(6) Da) complex, and they co-immunoprecipitate from Drosophila extracts. These findings provide direct evidence for conservation of the SWI/SNF complex in higher eucaryotes and suggest that the Drosophila brm/snr1 complex plays an important role in maintaining homeotic gene transcription during development by counteracting the repressive effects of chromatin.

scholarly journals batman Interacts with Polycomb and trithorax Group Genes and Encodes a BTB/POZ Protein That Is Included in a Complex Containing GAGA Factor

2003 ◽  
Vol 23 (4) ◽  
pp. 1181-1195 ◽  
Author(s):  
M. Faucheux ◽  
J.-Y. Roignant ◽  
S. Netter ◽  
J. Charollais ◽  
C. Antoniewski ◽  
...  
Keyword(s):  
Polytene Chromosomes ◽  
Homeotic Genes ◽  
Gaga Factor ◽  
Interaction Domain ◽  
Sex Combs Reduced ◽  
Trithorax Group ◽  
Protein Protein Interaction ◽  
Polycomb Response Element ◽  
Activated State ◽  
Large Protein Family

ABSTRACT Polycomb and trithorax group genes maintain the appropriate repressed or activated state of homeotic gene expression throughout Drosophila melanogaster development. We have previously identified the batman gene as a Polycomb group candidate since its function is necessary for the repression of Sex combs reduced. However, our present genetic analysis indicates functions of batman in both activation and repression of homeotic genes. The 127-amino-acid Batman protein is almost reduced to a BTB/POZ domain, an evolutionary conserved protein-protein interaction domain found in a large protein family. We show that this domain is involved in the interaction between Batman and the DNA binding GAGA factor encoded by the Trithorax-like gene. The GAGA factor and Batman codistribute on polytene chromosomes, coimmunoprecipitate from nuclear embryonic and larval extracts, and interact in the yeast two-hybrid assay. Batman, together with the GAGA factor, binds to MHS-70, a 70-bp fragment of the bithoraxoid Polycomb response element. This binding, like that of the GAGA factor, requires the presence of d(GA)n sequences. Together, our results suggest that batman belongs to a subset of the Polycomb/trithorax group of genes that includes Trithorax-like, whose products are involved in both activation and repression of homeotic genes.

scholarly journals A 1-Megadalton ESC/E(Z) Complex from Drosophila That Contains Polycomblike and RPD3

2003 ◽  
Vol 23 (9) ◽  
pp. 3352-3362 ◽  
Author(s):  
Feng Tie ◽  
Jayashree Prasad-Sinha ◽  
Anna Birve ◽  
Åsa Rasmuson-Lestander ◽  
Peter J. Harte
Keyword(s):  
Glutathione Transferase ◽  
Insertion Site ◽  
Polytene Chromosomes ◽  
Gel Filtration ◽  
Polycomb Group ◽  
Homeotic Genes ◽  
Histone Binding ◽  
Polycomb Response Element ◽  
N Terminus

ABSTRACT Polycomb group (PcG) proteins are required to maintain stable repression of the homeotic genes and others throughout development. The PcG proteins ESC and E(Z) are present in a prominent 600-kDa complex as well as in a number of higher-molecular-mass complexes. Here we identify and characterize a 1-MDa ESC/E(Z) complex that is distinguished from the 600-kDa complex by the presence of the PcG protein Polycomblike (PCL) and the histone deacetylase RPD3. In addition, the 1-MDa complex shares with the 600-kDa complex the histone binding protein p55 and the PcG protein SU(Z)12. Coimmunoprecipitation assays performed on embryo extracts and gel filtration column fractions indicate that, during embryogenesis E(Z), SU(Z)12, and p55 are present in all ESC complexes, while PCL and RPD3 are associated with ESC, E(Z), SU(Z)12, and p55 only in the 1-MDa complex. Glutathione transferase pulldown assays demonstrate that RPD3 binds directly to PCL via the conserved PHD fingers of PCL and the N terminus of RPD3. PCL and E(Z) colocalize virtually completely on polytene chromosomes and are associated with a subset of RPD3 sites. As previously shown for E(Z) and RPD3, PCL and SU(Z)12 are also recruited to the insertion site of a minimal Ubx Polycomb response element transgene in vivo. Consistent with these biochemical and cytological results, Rpd3 mutations enhance the phenotypes of Pcl mutants, further indicating that RPD3 is required for PcG silencing and possibly for PCL function. These results suggest that there may be multiple ESC/E(Z) complexes with distinct functions in vivo.

scholarly journals The Drosophila ash1 Gene Product, Which Is Localized at Specific Sites on Polytene Chromosomes, Contains a SET Domain and a PHD Finger

Genetics ◽  
1996 ◽  
Vol 143 (2) ◽  
pp. 913-928 ◽  
Author(s):  
Nicholas Tripoulas ◽  
Dennis LaJeunesse ◽  
John Gildea ◽  
Allen Shearn
Keyword(s):  
Amino Acids ◽  
Polytene Chromosomes ◽  
Protein Product ◽  
Polycomb Group ◽  
Transcriptional Level ◽  
Set Domain ◽  
Trithorax Group ◽  
Phd Finger ◽  
Polycomb Group Genes ◽  
The Stability

Abstract The determined state of Drosophila imaginal discs depends on stable patterns of homeotic gene expression. The stability of these patterns requires the function of the ash1 gene, a member of the trithorax group. The primary translation product of the 7.5-kb ash1 transcript is predicted to be a basic protein of 2144 amino acids. The ASHl protein contains a SET domain and a PHD finger. Both of these motifs are found in the products of some trithorax group and Polycomb group genes. We have determined the nucleotide sequence alterations in 10 ash1 mutant alleles and have examined their mutant phenotype. The best candidate for a null allele is ashl  22. The truncated protein product of this mutant allele is predicted to contain only 47 amino acids. The ASHl protein is localized on polytene chromosomes of larval salivary glands at >100 sites. The chromosomal localization of ASHl implies that it functions at the transcriptional level to maintain the expression pattern of homeotic selector genes.

The Drosophila GenetaranisEncodes a Novel Trithorax Group Member Potentially Linked to the Cell Cycle Regulatory Apparatus

Genetics ◽  
2002 ◽  
Vol 160 (2) ◽  
pp. 547-560 ◽  
Author(s):  
Stéphane Calgaro ◽  
Muriel Boube ◽  
David L Cribbs ◽  
Henri-Marc Bourbon
Keyword(s):  
Cell Cycle ◽  
Chromatin Structure ◽  
Protein A ◽  
Protein Isoforms ◽  
Alternative Promoters ◽  
Loss Of Function ◽  
Trithorax Group ◽  
Evolutionarily Conserved ◽  
Cycle Regulation ◽  
Group Member

AbstractGenes of the Drosophila Polycomb and trithorax groups (PcG and trxG, respectively) influence gene expression by modulating chromatin structure. Segmental expression of homeotic loci (HOM) initiated in early embryogenesis is maintained by a balance of antagonistic PcG (repressor) and trxG (activator) activities. Here we identify a novel trxG family member, taranis (tara), on the basis of the following criteria: (i) tara loss-of-function mutations act as genetic antagonists of the PcG genes Polycomb and polyhomeotic and (ii) they enhance the phenotypic effects of mutations in the trxG genes trithorax (trx), brahma (brm), and osa. In addition, reduced tara activity can mimic homeotic loss-of-function phenotypes, as is often the case for trxG genes. tara encodes two closely related 96-kD protein isoforms (TARA-α/-β) derived from broadly expressed alternative promoters. Genetic and phenotypic rescue experiments indicate that the TARA-α/-β proteins are functionally redundant. The TARA proteins share evolutionarily conserved motifs with several recently characterized mammalian nuclear proteins, including the cyclin-dependent kinase regulator TRIP-Br1/p34SEI-1, the related protein TRIP-Br2/Y127, and RBT1, a partner of replication protein A. These data raise the possibility that TARA-α/-β play a role in integrating chromatin structure with cell cycle regulation.

Telomeric Associated Sequences of Drosophila Recruit Polycomb-Group Proteins in Vivo and Can Induce Pairing-Sensitive Repression

Genetics ◽  
2003 ◽  
Vol 164 (1) ◽  
pp. 195-208 ◽  
Author(s):  
Antoine Boivin ◽  
Christelle Gally ◽  
Sophie Netter ◽  
Dominique Anxolabéhère ◽  
Stéphane Ronsseray
Keyword(s):  
Position Effect ◽  
Insertion Site ◽  
Polytene Chromosomes ◽  
Polycomb Group ◽  
Dependent Manner ◽  
Trithorax Group ◽  
Telomeric Silencing ◽  
Associated Sequences ◽  
Specific Factors

Abstract In Drosophila, relocation of a euchromatic gene near centromeric or telomeric heterochromatin often leads to its mosaic silencing. Nevertheless, modifiers of centromeric silencing do not affect telomeric silencing, suggesting that each location requires specific factors. Previous studies suggest that a subset of Polycomb-group (PcG) proteins could be responsible for telomeric silencing. Here, we present the effect on telomeric silencing of 50 mutant alleles of the PcG genes and of their counteracting trithorax-group genes. Several combinations of two mutated PcG genes impair telomeric silencing synergistically, revealing that some of these genes are required for telomeric silencing. In situ hybridization and immunostaining experiments on polytene chromosomes revealed a strict correlation between the presence of PcG proteins and that of heterochromatic telomeric associated sequences (TASs), suggesting that TASs and PcG complexes could be associated at telomeres. Furthermore, lines harboring a transgene containing an X-linked TAS subunit and the mini-white reporter gene can exhibit pairing-sensitive repression of the white gene in an orientation-dependent manner. Finally, an additional binding site for PcG proteins was detected at the insertion site of this type of transgene. Taken together, these results demonstrate that PcG proteins bind TASs in vivo and may be major players in Drosophila telomeric position effect (TPE).

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