scholarly journals Interactions of polyhomeotic with Polycomb group genes of Drosophila melanogaster.

Genetics ◽  
1994 ◽  
Vol 138 (4) ◽  
pp. 1151-1162 ◽  
Author(s):  
N N Cheng ◽  
D A Sinclair ◽  
R B Campbell ◽  
H W Brock
Keyword(s):  
Synergistic Effects ◽  
Polycomb Group ◽  
Mass Action ◽  
Temperature Sensitive ◽  
Homeotic Genes ◽  
Phenotypic Analysis ◽  
Group Function ◽  
Polycomb Group Genes ◽  
Multimeric Complex ◽  
Sex Combs

Abstract The Polycomb (Pc) group genes of Drosophila are negative regulators of homeotic genes, but individual loci have pleiotropic phenotypes. It has been suggested that Pc group genes might form a regulatory hierarchy, or might be members of a multimeric complex that obeys the law of mass action. Recently, it was shown that polyhomeotic (ph) immunoprecipitates in a multimeric complex that includes Pc. Here, we show that duplications of ph suppress homeotic transformations of Pc and Pcl, supporting a mass-action model for Pc group function. We crossed ph alleles to all members of the Polycomb group, and to E(Pc) and Su(z)2 to look for synergistic effects. We observed extragenic noncomplementation between ph503 and Pc, Psc1 and Su(z)2(1) in females, and between ph409 and Sce1, ScmD1 and E(z)1 mutations in males, suggesting that these gene products might interact directly with ph. Males hemizygous for a temperature-sensitive allele, ph2, are lethal when heterozygous with mutants in Asx, Pc, Pcl, Psc, Sce and Scm, and with E(Pc) and Su(z)2. Mutations in trithorax group genes were not able to suppress the lethality of ph2/Y; Psc1/+ males. ph2 was not lethal with extra sex combs, E(z), super sex combs (sxc) or l(4)102EFc heterozygotes, but did cause earlier lethality in embryos homozygous for E(z), sxc and l(4)102EFc. However, ph503 did not enhance homeotic phenotypes of esc heterozygotes derived from homozygous esc- mothers. We examined the embryonic phenotypes of ph2 embryos that were lethal when heterozygous or homozygous for other mutations. Based on this phenotypic analysis, we suggest that ph may perform different functions in conjunction with differing subsets of Pc group genes.

Maintenance of the engrailed expression pattern by Polycomb group genes in Drosophila

Development ◽  
1992 ◽  
Vol 116 (3) ◽  
pp. 805-810 ◽  
Author(s):  
D. Moazed ◽  
P.H. O'Farrell
Keyword(s):  
Expression Pattern ◽  
Expression Patterns ◽  
Ectopic Expression ◽  
Polycomb Group ◽  
Homeotic Genes ◽  
Polycomb Group Genes ◽  
Sex Combs ◽  
Segment Polarity ◽  
Selector Genes ◽  
Stable Maintenance

The stable maintenance of expression patterns of homeotic genes depends on the function of a number of negative trans-regulators, termed the Polycomb (Pc) group of genes. We have examined the pattern of expression of the Drosophila segment polarity gene, engrailed (en), in embryos mutant for several different members of the Pc group. Here we report that embryos mutant for two or more Pc group genes show strong ectopic en expression, while only weak derepression of en occurs in embryos mutant for a single Pc group gene. This derepression is independent of two known activators of en expression: en itself and wingless. Additionally, in contrast to the strong ectopic expression of homeotic genes observed in extra sex combs- (esc-) mutant embryos, the en expression pattern is nearly normal in esc- embryos. This suggests that the esc gene product functions in a pathway independent of the other genes in the group. The data indicate that the same group of genes is required for stable restriction of en expression to a striped pattern and for the restriction of expression of homeotic genes along the anterior-posterior axis, and support a global role for the Pc group genes in stable repression of activity of developmental selector genes.

scholarly journals Needs and Targets for the multi sex combs Gene Product in Drosophila melanogaster

Genetics ◽  
1998 ◽  
Vol 149 (4) ◽  
pp. 1823-1838 ◽  
Author(s):  
Olivier Saget ◽  
Françoise Forquignon ◽  
Pedro Santamaria ◽  
Neel B Randsholt
Keyword(s):  
Drosophila Melanogaster ◽  
Ectopic Expression ◽  
Polycomb Group ◽  
Homeotic Genes ◽  
Maternal Control ◽  
Gap Gene ◽  
Sex Combs ◽  
Normal Expression ◽  
Selector Genes ◽  
Mutant Phenotypes

Abstract We have analyzed the requirements for the multi sex combs (mxc) gene during development to gain further insight into the mechanisms and developmental processes that depend on the important trans-regulators forming the Polycomb group (PcG) in Drosophila melanogaster. mxc is allelic with the tumor suppressor locus lethal (1) malignant blood neoplasm (l(1)mbn). We show that the mxc product is dramatically needed in most tissues because its loss leads to cell death after a few divisions. mxc has also a strong maternal effect. We find that hypomorphic mxc mutations enhance other PcG gene mutant phenotypes and cause ectopic expression of homeotic genes, confirming that PcG products are cooperatively involved in repression of selector genes outside their normal expression domains. We also demonstrate that the mxc product is needed for imaginal head specification, through regulation of the ANT-C gene Deformed. Our analysis reveals that mxc is involved in the maternal control of early zygotic gap gene expression previously reported for some PcG genes and suggests that the mechanism of this early PcG function could be different from the PcG-mediated regulation of homeotic selector genes later in development. We discuss these data in view of the numerous functions of PcG genes during development.

scholarly journals Molecular characterisation of the Polycomblike gene of Drosophila melanogaster, a trans-acting negative regulator of homeotic gene expression

Development ◽  
1994 ◽  
Vol 120 (9) ◽  
pp. 2629-2636 ◽  
Author(s):  
A. Lonie ◽  
R. D'Andrea ◽  
R. Paro ◽  
R. Saint
Keyword(s):  
Gene Expression ◽  
Drosophila Melanogaster ◽  
Polycomb Group ◽  
Negative Regulator ◽  
Homeotic Gene ◽  
Homeotic Genes ◽  
Molecular Characterisation ◽  
Polycomb Group Proteins ◽  
Polycomb Group Genes ◽  
Homeotic Gene Expression

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.

scholarly journals Genetic analysis of the enhancer of zeste locus and its role in gene regulation in Drosophila melanogaster.

Genetics ◽  
1990 ◽  
Vol 126 (1) ◽  
pp. 185-199 ◽  
Author(s):  
R S Jones ◽  
W M Gelbart
Keyword(s):  
Gene Regulation ◽  
Drosophila Melanogaster ◽  
Ectopic Expression ◽  
Polycomb Group ◽  
Temperature Sensitive ◽  
Loss Of Function ◽  
Eye Color ◽  
Polycomb Group Genes ◽  
Enhancer Of Zeste ◽  
Gene Complexes

Abstract The Enhancer of zeste [E(z)] locus of Drosophila melanogaster is implicated in multiple examples of gene regulation during development. First identified as dominant gain-of-function modifiers of the zeste1-white (z-w) interaction, mutant E(z) alleles also produce homeotic transformations. Reduction of E(z)+ activity leads to both suppression of the z-w interaction and ectopic expression of segment identity genes of the Antennapedia and bithorax gene complexes. This latter effect defines E(z) as a member of the Polycomb-group of genes. Analysis of E(z)S2, a temperature-sensitive E(z) allele, reveals that both maternally and zygotically produced E(z)+ activity is required to correctly regulate the segment identity genes during embryonic and imaginal development. As has been shown for other Polycomb-group genes, E(z)+ is required not to initiate the pattern of these genes, but rather to maintain their repressed state. We propose that the E(z) loss-of-function eye color and homeotic phenotypes may both be due to gene derepression, and that the E(z)+ product may be a general repressing factor required for both examples of negative gene regulation.

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.

Ten different Polycomb group genes are required for spatial control of the abdA and AbdB homeotic products

Development ◽  
1992 ◽  
Vol 114 (2) ◽  
pp. 493-505 ◽  
Author(s):  
J. Simon ◽  
A. Chiang ◽  
W. Bender
Keyword(s):  
Expression Patterns ◽  
Ectopic Expression ◽  
Specific Pattern ◽  
Polycomb Group ◽  
Polycomb Group Genes ◽  
Sex Combs ◽  
Normal Expression ◽  
Sex Comb ◽  
Regulatory Dna ◽  
Pair Rule

Mutations in genes of the Polycomb (Pc) group cause abnormal segmental development due to ectopic expression of the homeotic products of the Antennapedia and bithorax complexes. Here the requirements for Pc group genes in controlling the abdA and AbdB products of the bithorax complex are described. Embryos containing mutations in the genes Polycomb (Pc), extra sex combs (esc), Enhancer of zeste [E(z)], polyhomeotic (ph), Sex comb on midleg (Scm), Polycomb-like (Pcl), Sex comb extra (Sce), Additional sex combs (Asx), Posterior sex combs (Psc) and pleiohomeotic (pho) were examined. In every case, both abdA and AbdB are expressed outside of their normal domains along the anterior-posterior (A-P) axis, consistent with these Pc group products acting in a single pathway or molecular complex. The earliest detectable ectopic expression is highest in the parasegments immediately adjacent to the normal expression boundary. Surprisingly, in the most severe Pc group mutants, the earliest ectopic AbdB is distributed in a pair-rule pattern. At all stages, ectopic abdA in the epidermis is highest along the anterior edges of the parasegments, in a pattern that mimics the normal abdA cell-specific pattern. These examples of highly patterned mis-expression show that Pc group mutations do not cause indiscriminate activation of homeotic products. We suggest that the ectopic expression patterns result from factors that normally activate abdA and AbdB only in certain parasegments, but that in Pc group mutants these factors gain access to regulatory DNA in all parasegments.

The Drosophila Polycomb Group proteins ESC and E(Z) bind directly to each other and co-localize at multiple chromosomal sites

Development ◽  
1998 ◽  
Vol 125 (17) ◽  
pp. 3483-3496 ◽  
Author(s):  
F. Tie ◽  
T. Furuyama ◽  
P.J. Harte
Keyword(s):  
Polycomb Group ◽  
Homeotic Genes ◽  
Polycomb Group Proteins ◽  
Polycomb Group Protein ◽  
Polycomb Group Genes ◽  
Evolutionarily Conserved ◽  
Group Protein ◽  
Essential Prerequisite

The Polycomb Group gene esc encodes an evolutionarily conserved protein required for transcriptional silencing of the homeotic genes. Unlike other Polycomb Group genes, esc is expressed and apparently required only during early embryogenesis, suggesting it is required for the initial establishment of silencing but not for its subsequent maintenance. We present evidence that the ESC protein interacts directly with E(Z), another Polycomb Group protein required for silencing of the homeotic genes. We show that the most highly conserved region of ESC, containing seven WD motifs that are predicted to fold into a beta-propeller structure, mediate its binding to a conserved N-terminal region of E(Z). Mutations in the WD region that perturb ESC silencing function in vivo also perturb binding to E(Z) in vitro. The entire WD region forms a trypsin-resistant structure, like known beta -propeller domains, and mutations that would affect the predicted ESC beta-propeller perturb its trypsin-resistance, while a putative structure-conserving mutation does not. We show by co-immunoprecipitation that ESC and E(Z) are directly associated in vivo and that they also co-localize at many chromosomal binding sites. Since E(Z) is required for binding of other Polycomb Group proteins to chromosomes, these results suggest that formation of an E(Z):ESC complex at Polycomb Response Elements may be an essential prerequisite for the establishment of silencing.

scholarly journals Mutations in polycombeotic, a Drosophila polycomb-group gene, cause a wide range of maternal and zygotic phenotypes.

Genetics ◽  
1990 ◽  
Vol 125 (1) ◽  
pp. 91-101 ◽  
Author(s):  
M D Phillips ◽  
A Shearn
Keyword(s):  
Extreme Temperature ◽  
Polycomb Group ◽  
Null Alleles ◽  
Temperature Sensitive ◽  
Restrictive Temperature ◽  
Polycomb Group Genes ◽  
Wide Range ◽  
Small Disc ◽  
Sensitive Allele ◽  
Anterior Segments

Abstract The polycomb-group genes, a set of genes characterized by mutations that cause similar phenotypes and dosage-dependent interactions, are required for the normal expression of segment-specific homeotic loci. Here we report that polycombeotic (formerly 1(3)1902), originally identified by a lethal mutation that causes a small-disc phenotype, is also a member of this group of essential genes. Adults homozygous for temperature-sensitive pco alleles that were exposed to the restrictive temperature during larval life display the second and third leg to first leg transformation characteristic of polycomb-group mutants. Adult females homozygous for temperature-sensitive alleles exposed to the restrictive temperature during oogenesis produce embryos that show anterior segments with structures normally unique to the eighth abdominal segment, another transformation characteristic of polycomb-group mutants. Mutations in the polycombeotic gene also cause defects not reported for mutations in other polycomb-group genes. Females homozygous for the most extreme temperature-sensitive allele are sterile, and larvae homozygous for null alleles have small imaginal discs and reduced frequencies of mitotic figures in the brain. Dominant mutations originally identified as enhancers or suppressors of zeste are gain-of-function alleles of polycombeotic. The type and variety of defects displayed by different mutations in this gene indicate that the product might be involved in chromosome structure and/or function.

scholarly journals The polycomb group protein complex of Drosophila melanogaster has different compositions at different target genes.

1997 ◽  
Vol 17 (12) ◽  
pp. 6773-6783 ◽  
Author(s):  
H Strutt ◽  
R Paro
Keyword(s):  
Protein Complex ◽  
Target Genes ◽  
Regulatory Elements ◽  
Polycomb Group ◽  
Regulatory Sequences ◽  
Polycomb Group Protein ◽  
Polycomb Group Genes ◽  
Sex Combs ◽  
Group Protein

In Drosophila the Polycomb group genes are required for the long-term maintenance of the repressed state of many developmental regulatory genes. Their gene products are thought to function in a common multimeric complex that associates with Polycomb group response elements (PREs) in target genes and regulates higher-order chromatin structure. We show that the chromodomain of Polycomb is necessary for protein-protein interactions within a Polycomb-Polyhomeotic complex. In addition, Posterior Sex Combs protein coimmunoprecipitates Polycomb and Polyhomeotic, indicating that they are members of a common multimeric protein complex. Immunoprecipitation experiments using in vivo cross-linked chromatin indicate that these three Polycomb group proteins are associated with identical regulatory elements of the selector gene engrailed in tissue culture cells. Polycomb, Polyhomeotic, and Posterior Sex Combs are, however, differentially distributed on regulatory sequences of the engrailed-related gene invected. This suggests that there may be multiple different Polycomb group protein complexes which function at different target sites. Furthermore, Polyhomeotic and Posterior Sex Combs are also associated with expressed genes. Polyhomeotic and Posterior Sex Combs may participate in a more general transcriptional mechanism that causes modulated gene repression, whereas the inclusion of Polycomb protein in the complex at PREs leads to stable silencing.

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.

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