PubMed Health⌕ Search

Biomedical subjects

T I Gerasimova

Publications and source records attributed to T I Gerasimova.

At least 19 recordsLinked to original sources

Interactions between the Su(Hw) and Mod(mdg4) proteins required for gypsy insulator function.

The gypsy insulator is thought to play a role in nuclear organization and the establishment of higher order chromatin domains by bringing together several individual insulator sites to form rosette-like structures in the interphase nucleus. The Su(Hw) and Mod(mdg4) proteins are components of the gypsy insulator required for its effect on enhancer-promoter interactions. Using the yeast two-hybrid system, we show that the Mod(mdg4) protein can form homodimers, which can then interact with Su(Hw). The BTB domain of Mod(mdg4) is involved in homodimerization, whereas the C-terminal region of the protein is involved in interactions with the leucine zipper and adjacent regions of the Su(Hw) protein. Analyses using immunolocalization on polytene chromosomes confirm the involvement of these domains in mediating the interactions between these proteins. Studies using diploid interphase cells further suggest the contribution of these domains to the formation of rosette-like structures in the nucleus. The results provide a biochemical basis for the aggregation of multiple insulator sites and support the role of the gypsy insulator in nuclear organization.

Animals↗

Chromatin insulators and boundaries: effects on transcription and nuclear organization.

Chromatin boundaries and insulators are transcriptional regulatory elements that modulate interactions between enhancers and promoters and protect genes from silencing effects by the adjacent chromatin. Originally discovered in Drosophila, insulators have now been found in a variety of organisms, ranging from yeast to humans. They have been found interspersed with regulatory sequences in complex genes and at the boundaries between active and inactive chromatin. Insulators might modulate transcription by organizing the chromatin fiber within the nucleus through the establishment of higher-order domains of chromatin structure.

Animals↗

A chromatin insulator determines the nuclear localization of DNA.

Chromatin insulators might regulate gene expression by controlling the subnuclear organization of DNA. We found that a DNA sequence normally located inside of the nucleus moved to the periphery when the gypsy insulator was placed within the sequence. The presence of the gypsy insulator also caused two sequences, normally found in different regions of the nucleus, to come together at a single location. Alterations in this subnuclear organization imposed by the gypsy insulator correlated with changes in gene expression that took place during the heat-shock response. These global changes in transcription were accompanied by dramatic alterations in the distribution of insulator proteins and DNA. The results suggest that the nuclear organization imposed by the gypsy insulator on the chromatin fiber is important for gene expression.

Animals↗

The lawc gene is a new member of the trithorax-group that affects the function of the gypsy insulator of Drosophila.

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.

Animals↗

Polycomb and trithorax group proteins mediate the function of a chromatin insulator.

Chromatin boundaries or insulator elements affect the interaction between enhancers and promoters. The gypsy insulator contains two proteins, Su(Hw) and Mod(mdg4). Both proteins colocalize on several hundred sites on polytene chromosomes and are distributed in a punctated pattern in the nuclear matrix. Mutations in mod(mdg4) have properties characteristic of a trxG gene. In addition, mutations in trxG genes enhance insulator effects on adjacent enhancers, whereas mutations in Pc have the opposite result. These alterations correlate with changes in the pattern of nuclear localization of insulator components. The results suggest a model in which PcG and TrxG proteins regulate insulator function by establishing higher order domains of chromatin organization required for the assembly of functional insulators at the nuclear matrix.

Animals↗

Genetic and molecular analysis of the gypsy chromatin insulator of Drosophila.

Boundary or insulator elements set up independent territories of gene activity by establishing higher order domains of chromatin structure. The gypsy retrotransposon of Drosophila contains an insulator element that represses enhancer-promoter interactions and is responsible for the mutant phenotypes caused by insertion of this element. The gypsy insulator inhibits the interaction of promoter-distal enhancers with the transcription complex without affecting the functionality of promoter-proximal enhancers; in addition, these sequences can buffer a transgene from chromosomal position effects. Two proteins have been identified that bind gypsy insulator sequences and are responsible for their effects on transcription. The suppressor of Hairy-wing [su(Hw)] protein affects enhancer function both upstream and downstream of its binding site by causing a silencing effect similar to that of heterochromatin. The modifier of mdg4 [mod(mdg4)] protein interacts with su(Hw) to transform this bi-directional repression into the polar effect characteristic of insulators. These effects seem to be modulated by changes in chromatin structure.

Animals↗

Boundary and insulator elements in chromosomes.

Recent progress in understanding boundary and insulator elements has concentrated on the identification of their protein components. BEAF-32 is a protein present in the scs' element of Drosophila that is also localized to most interband regions and puffs of polytene chromosomes, suggesting a role in the organization of structural chromosomal domains. The suppressor of Hairy-wing and modifier of mdg4 proteins have been characterized as components of the gypsy insulator. The latter seems to play a crucial role in conferring on the insulator its ability to unidirectionally affect enhancer function.

Animals↗

A Drosophila protein that imparts directionality on a chromatin insulator is an enhancer of position-effect variegation.

The suppressor of Hairy wing (su(Hw)) protein inhibits the function of transcriptional enhancers located distally from the promoter with respect to the location of su(Hw)-binding sites. This polarity is due to the ability of the su(Hw)-binding region to form a chromatin insulator. Mutations in modifier of mdg4 (mod(mdg4)) enhance the effect of su(Hw) by inhibiting the function of enhancers located on both sides of the su(Hw)-binding region. This inhibition results in a variegated expression pattern, and mutations in mod(mdg4) act as classical enhancers of position-effect variegation. The mod(mdg4) and su(Hw) proteins interact with each other. The mod(mdg4) protein controls the nature of the repressive effect of su(Hw): in the absence of mod(mdg4) protein, su(Hw) exerts a bidirectional silencing effect, whereas in the presence of mod(mdg4), the silencing effect is transformed into unidirectional repression.

Alleles↗

[Determination of a temperature-sensitive period of the new mutation lawc(P1) in Drosophila melanogaster].

Determination of the period of temperature sensitivity in the temperature-sensitive allele of the regulatory lawc(P1) mutation was performed. Homeotic transformation of arista into tarsus, frequency of leg deformation, and bristle superexpression were examined. The sensitive periods were detected using reciprocal changes of cultivation temperature from 28 to 17 degrees C and from 17 to 28 degrees C. The temperature-sensitive period (TSP) for arista transformation was shown to manifest polyphasic expression and sexual dimorphism. In females, it occurred in late third instar larvae (the first phase) and prepupae (the second stage); in males, it includes the whole period from the late third instar larva upto and including prepupa. TSP for the frequency of deformed legs was polyphasic and took place during the third larval instar (the first phase) and prepupa stage (the second one). TSP for bristle superexpression occurred during a single interval from the late third larval instar until the early prepupa stage. The products of the lawc gene are assumed to play a role both in the cell proliferation in the legs of antennal and imaginal discs and in the control of bristle expression at the final stages of Drosophila ontogeny.

Alleles↗

[Complex instability in the system of hobo and stalker mobile element interaction in Drosophila melanogaster].

A number of mutations in different Drosophila loci resulted from the relationship between hobo and stalker mobile elements. In this investigation an insertion from the parential white mutation-waG-was cloned. And the Doc element, that is the reason of the mutation, is not moving in the observed instability system. But transpositions of the copia-like elements (e.g. mdg1, 2, 3 and copia) were shown in this system. A cases of chromosomal rearrangements and abnormal recombination in compound with transpositions of different mobile elements were found. Thus, the system of instability could be explained in terms of universal mechanism which involved both transpositions and recombinations phenomena.

Alleles↗

Intragenic suppression: Stalker, a retrovirus-like transposable element, can compensate for a deficiency at the cut locus of Drosophila melanogaster.

A number of mutations at the cut locus were induced by non-precise excision of a silent P-element insertion which resulted in deletions at the regulatory region of the locus. Unexpectedly, a reversion of one of these mutations was found, which appears as a result of insertion of Stalker (a retrovirus-like mobile element) near the 1.3 kb deletion. Thus an insertion of a retrovirus-like mobile element can suppress the deficiency at the regulatory region of a gene.

Animals↗

Dominant effects of suppressor of Hairy-wing mutations on gypsy-induced alleles of forked and cut in Drosophila melanogaster.

Mutations induced by the gypsy retrotransposon in the forked (f) and cut (ct) loci render their expression under the control of the suppressor of Hairy-wing [su(Hw)] gene. This action is usually recessive, but su(Hw) acts as a dominant on the alleles fk, ctk and ctMRpN30. Molecular analysis of the gypsy element present in fk indicates that this allele is caused by the insertion of a modified gypsy in which the region normally containing twelve copies of the octamer-like repeat that interacts with the su(Hw) product is altered. Analysis of the gypsy element responsible for the ctk and ctMRpN30 mutations also reveals a correlation between the dominant action of su(Hw) and disruption of the octamer region. We propose that these disruptions alter the affinity and interaction of su(Hw) protein with gypsy DNA, thereby sensitizing the mutant phenotype to fluctuations in su(Hw) product.

Alleles↗

[Participation of mobile element hobo in transposition events in the long-term instability system of Drosophila melanogaster].

The lines with an active hobo elements as well as those without any hobo fragments were hybridized with the y2sc1waG line. This resulted in the appearance of a number of mutations at the white, miniature, and some other loci. The authors analysed, in which way the hobo transposable elements take part in mutagenesis in these crosses. Most of the white mutants obtained were analysed and transpositions of hobo and Stalker elements were demonstrated. Both independent and simultaneous transpositions were found. It was shown by means of the Southern blot analysis that additional hobo or Stalker insertion into or close to the parental unknown waG insertion resulted in mutant white phenotype's shift toward both extreme and partial reversion. Possible participation in mutagenesis of other mobile elements is also under debate.

Animals↗

[Suppressor mutation, interacting with the white alleles of Drosophila melanogaster].

A system of genetic instability was developed by crosses of males y2 wa4 with females C(1)DX, ywf. Mutations occurred in the second and third generations with the rate 0.7.10(-3)-1.5.10(-3). A novel gene named Suppressor of wa4--Su(wa4) was selected in this system. The Su(wa4)M1 is dominant and was localised in the position of 309 map units. Su(wa4)M1 suppressed wa, wa4, wbf, waG which had insertions of different transposable elements in different introns of the white locus. However, Su(wa4) does not interact with other w mutations. So, we suggested that Su(wa4) is trans-regulatory gene and its product involves in the expression regulation the white locus, probably, on the transcriptional level.

Alleles↗

[Induction of unstable mutations in Drosophila melanogaster by microinjection of oncogenic virus DNA into the embryo polar plasma. Insertional nature of mutations].

We have demonstrated that mutations induced in Drosophila melanogaster by the microinjections of adenovirus Sa7 DNA in early embryos are of insertional nature. The role of insertional elements is played by the Drosophila transposons, but not by the virus DNA. The ability of oncoviral DNA to induce transpositions of mobile elements in recipient genome is the molecular basis of this system of genetic instability.

Adenoviridae↗