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.

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 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.

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.

Identification of Polycomb and trithorax group responsive elements in the regulatory region of the Drosophila homeotic gene Sex combs reduced.

Genetics ◽  
1995 ◽  
Vol 139 (2) ◽  
pp. 797-814 ◽  
Author(s):  
J G Gindhart ◽  
T C Kaufman
Keyword(s):  
Regulatory Region ◽  
Polycomb Group ◽  
Homeotic Gene ◽  
Regulatory Sequences ◽  
Dependent Manner ◽  
Gene Products ◽  
Dna Fragments ◽  
Sex Combs Reduced ◽  
Trithorax Group ◽  
Sex Combs

Abstract The Drosophila homeotic gene Sex combs reduced (Scr) is necessary for the establishment and maintenance of the morphological identity of the labial and prothoracic segments. In the early embryo, its expression pattern is established through the activity of several gap and segmentation gene products, as well as other transcription factors. Once established, the Polycomb group (Pc-G) and trithorax group (trx-G) gene products maintain the spatial pattern of Scr expression for the remainder of development. We report the identification of DNA fragments in the Scr regulatory region that may be important for its regulation by Polycomb and trithorax group gene products. When DNA fragments containing these regulatory sequences are subcloned into P-element vectors containing a white minigene, transformants containing these constructs exhibit mosaic patterns of pigmentation in the adult eye, indicating that white minigene expression is repressed in a clonally heritable manner. The size of pigmented and nonpigmented clones in the adult eye suggests that the event determining whether a cell in the eye anlagen will express white occurs at least as early as the first larval instar. The amount of white minigene repression is reduced in some Polycomb group mutants, whereas repression is enhanced in flies mutant for a subset of trithorax group loci. The repressor activity of one fragment, normally located in Scr Intron 2, is increased when it is able to homologously pair, a property consistent with genetic data suggesting that Scr exhibits transvection. Another Scr regulatory fragment, normally located 40 kb upstream of the Scr promoter, silences ectopic expression of an Scr-lacZ fusion gene in the embryo and does so in a Polycomb-dependent manner. We propose that the regulatory sequences located within these DNA fragments may normally mediate the regulation of Scr by proteins encoded by members of the Polycomb and trithorax group loci.

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 Genetic analysis of the additional sex combs locus of Drosophila melanogaster.

Genetics ◽  
1992 ◽  
Vol 130 (4) ◽  
pp. 817-825 ◽  
Author(s):  
D A Sinclair ◽  
R B Campbell ◽  
F Nicholls ◽  
E Slade ◽  
H W Brock
Keyword(s):  
Drosophila Melanogaster ◽  
Chromatin Structure ◽  
Polycomb Group ◽  
Homeotic Genes ◽  
Sex Combs ◽  
Normal Expression ◽  
Additional Sex Combs ◽  
Unusual Phenotype ◽  
New Alleles

Abstract Additional sex combs (Asx) is a member of the Polycomb group of genes, which are thought to be required for maintenance of chromatin structure. To better understand the function of Asx, we have isolated nine new alleles, each of which acts like a gain of function mutation. Asx is required for normal determination of segment identity. AsxP1 shows an unusual phenotype in that anterior and posterior homeotic transformations are seen in the same individuals, suggesting that AsxP1 might upset chromatin structure in a way that makes both activation and repression of homeotic genes more difficult. Analysis of embryonic and adult phenotypes of Asx alleles suggests that Asx is required zygotically for determination of segment number and polarity. The expression pattern of even-skipped is altered in Asx mutant embryos, suggesting that Asx is required for normal expression of this gene. We have transposon-tagged the Asx gene, and can thus begin molecular analysis of its function.

Homeotic complex and teashirt genes co-operate to establish trunk segmental identities in Drosophila

Development ◽  
1994 ◽  
Vol 120 (8) ◽  
pp. 2287-2296 ◽  
Author(s):  
P. de Zulueta ◽  
E. Alexandre ◽  
B. Jacq ◽  
S. Kerridge
Keyword(s):  
Heat Shock ◽  
Target Genes ◽  
Homeotic Genes ◽  
Sex Combs Reduced ◽  
Downstream Target ◽  
Functional Aspects ◽  
Sex Combs ◽  
Head Segment ◽  
Posterior Trunk ◽  
Segmental Identity

Homeotic genes determine the identities of metameres in Drosophila. We have examined functional aspects of the homeotic gene teashirt by ectopically expressing its product under the control of a heat-shock promoter during embryogenesis. Our results confirm that the gene is critical for segmental identity of the larva. Under mild heat-shock conditions, the Teashirt protein induces an almost complete transformation of the labial to prothoracic segmental identity, when expressed before 8 hours of development. Positive autoregulation of the endogenous teashirt gene and the presence of Sex combs reduced protein in the labium explain this homeosis. Patterns in the maxillary and a more anterior head segment are partly replaced with trunk ones. Additional Teashirt protein has no effect on the identity of the trunk segments where the gene is normally expressed; teashirt function is overridden by some homeotic complex acting in the posterior trunk. Strong heat-shock regimes provoke novel defects: ectopic sense organs differentiate in posterior abdominal segments and trunk pattern elements differentiate in the ninth abdominal segment. Teashirt acts in a partially redundant way with certain homeotic complex proteins but co-operates with them for the establishment of specific segment types. We suggest that Teashirt and HOM-C proteins regulate common sets of downstream target genes.

Ectopic expression of homeotic genes caused by the elimination of the Polycomb gene in Drosophila imaginal epidermis

Development ◽  
1988 ◽  
Vol 104 (4) ◽  
pp. 713-720 ◽  
Author(s):  
A. Busturia ◽  
G. Morata
Keyword(s):  
Ectopic Expression ◽  
Homeotic Genes ◽  
Sex Combs Reduced ◽  
Hierarchical Order ◽  
Sex Combs ◽  
Morphological Patterns

The morphological patterns in the adult cuticle of Drosophila are determined principally by the homeotic genes of the bithorax and Antennapedia complexes. We find that many of these genes become indiscriminately active in the adult epidermis when the Pc gene is eliminated. By using the Pc3 mutation and various BX-C mutant combinations, we have generated clones of imaginal cells possessing different combinations of active homeotic genes. We find that, in the absence of BX-C genes, Pc- clones develop prothoracic patterns; this is probably due to the activity of Sex combs reduced which overrules Antennapedia. Adding contributions of Ultrabithorax, abdominal-A and Abdominal-B results in thoracic or abdominal patterns. We have established a hierarchical order among these genes: Antp less than Scr less than Ubx less than abd-A less than Abd-B. In addition, we show that the engrailed gene is ectopically active in Pc- imaginal cells.

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