Influence of deficiency of the histone gene-containing 38B-40 region on X-chromosome template activity and the White gene position effect variegation in Drosophila melanogaster

Abstract Genomic imprinting is a phenomenon in which the expression of a gene or chromosomal region depends on the sex of the individual transmitting it. The term imprinting was first coined to describe parent-specific chromosome behavior in the dipteran insect Sciara and has since been described in many organisms, including other insects, plants, fish, and mammals. In this article we describe a mini-X chromosome in Drosophila melanogaster that shows genomic imprinting of at least three closely linked genes. The imprinting of these genes is observed as mosaic silencing when the genes are transmitted by the male parent, in contrast to essentially wild-type expression when the same genes are maternally transmitted. We show that the imprint is due to the sex of the parent rather than to a conventional maternal effect, differential mitotic instability of the mini-X chromosome, or an allele-specific effect. Finally, we have examined the effects of classical modifiers of position-effect variegation on the maintenance and the establishment of the imprint. Factors that modify position-effect variegation alter the somatic expression but not the establishment of the imprint. This suggests that chromatin structure is important in maintenance of the imprint, but a separate mechanism may be responsible for its initiation.

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Observations on the induction of position effect variegation of euchromatic genes in Drosophila melanogaster.

Genetics ◽

10.1093/genetics/134.1.231 ◽

1993 ◽

Vol 134 (1) ◽

pp. 231-242

Author(s):

G V Pokholkova ◽

I V Makunin ◽

E S Belyaeva ◽

I F Zhimulev

Keyword(s):

Drosophila Melanogaster ◽

Low Temperature ◽

X Chromosome ◽

Position Effect ◽

Complete Disappearance ◽

Position Effect Variegation ◽

Normal Phenotype ◽

Normal Expression ◽

Effect Variegation ◽

Heterochromatic Sequence

Abstract In the T(1;2)dorvar7 translocation, the 1A-2B7-8 segment of the X chromosome is brought to the vicinity of 2R-chromosome heterochromatin resulting in position effect variegation of dor, BR-C and more distal genes, as well as compaction of chromatin in this segment. By irradiation of T(1;2)dorvar7, nine reversions (rev) to a normal phenotype were recovered. In two cases (rev27, rev226), the 1A-2B7-8 section is relocated to the 19A region of the X chromosome, forming free duplications (1A-2B7-8/19A-20F-X-het). Modifiers of position effect do not change the normal expression of the BR-C and dor genes in these duplications. In five reversions (rev3, rev40, rev60, rev167, rev175), free duplications have formed from the 1A-2B7-8 fragment and X chromosome heterochromatin. In these rearrangements, modifiers of position effect (low temperature, removal of Y and 2R-chromosome heterochromatin and a genetic enhancer (E-var(3)201) induce position-effect again. Two reversions (rev45 and rev110) are associated with additional inversions in the original dorvar7 chromosomes. The inversions relocate part of the heterochromatin adjacent to the 1A-2B7-8 section into new positions. In T(1;2)dorrev45, position-effect is seen in the 2B7-8-7A element as compaction spreading from 2B7-8 proximally in some cases as far as the 5D region. Thus, in rev45 the pattern of euchromatin compaction is reciprocal to that of the initial dorvar7 strain. Apparently, it is due to the same variegation-evoking center near the 2R centromere in both cases. In all nine revertants, weakening or complete disappearance of the position-effect is observed despite retention of the 20-kb heterochromatic segment adjacent to the 1A-2B7-8 region. Thus, a 20-kb heterochromatic sequence does not inactivate euchromatin joined to it.

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HISTONE GENE MULTIPLICITY AND POSITION EFFECT VARIEGATION IN DROSOPHILA MELANOGASTER

Genetics ◽

10.1093/genetics/105.2.327 ◽

1983 ◽

Vol 105 (2) ◽

pp. 327-344

Author(s):

Gerald D Moore ◽

Donald A Sinclair ◽

Thomas A Grigliatti

Keyword(s):

Drosophila Melanogaster ◽

Sex Chromosome ◽

Current Knowledge ◽

Position Effect ◽

Histone Gene ◽

Position Effect Variegation ◽

Chromosome 2 ◽

Gene Complex ◽

Position Effects ◽

Effect Variegation

ABSTRACT The histone genes of wild-type Drosophila melanogaster are reiterated 100–150 times per haploid genome and are located in the segment of chromosome 2 that corresponds to polytene bands 39D2-3 to E1-2. The influence of altered histone gene multiplicity on chromatin structure has been assayed by measuring modification of the gene inactivation associated with position effect variegation in genotypes bearing deletions of the 39D-E segment. The proportion of cells in which a variegating gene is active is increased in genotypes that are heterozygous for a deficiency that removes the histone gene complex. Deletions that remove segments adjacent to the histone gene complex have no effect on the expression of variegating genes. Suppression of position effect variegation associated with reduction of histone gene multiplicity applies to both X-linked and autosomal variegating genes. Position effects exerted by both autosomal and sex-chromosome heterochromatin were suppressible by deletions of the histone gene complex. The suppression was independent of the presence of the Y chromosome. A deficiency that deletes only the distal portion of the histone gene complex also has the ability to suppress position effect variegation. Duplication of the histone gene complex did not enhance position effect variegation. Deletion or duplication of the histone gene complex in the maternal genome had no effect on the extent of variegation in progeny whose histone gene multiplicity was normal. These results are discussed with respect to current knowledge of the organization of the histone gene complex and control of its expression.

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MATERNAL-ZYGOTIC LETHAL INTERACTIONS IN DROSOPHILA MELANOGASTER: THE EFFECTS OF DEFICIENCIES IN THE ZESTE-WHITE REGION OF THE X CHROMOSOME

Genetics ◽

10.1093/genetics/96.1.187 ◽

1980 ◽

Vol 96 (1) ◽

pp. 187-200 ◽

Cited By ~ 1

Author(s):

Leonard G Robbins

Keyword(s):

Gene Expression ◽

Drosophila Melanogaster ◽

X Chromosome ◽

Position Effect ◽

Gene Activity ◽

Position Effect Variegation ◽

White Region ◽

Effect Variegation ◽

Zygotic Gene ◽

Maternal Gene

ABSTRACT The possibility that essential loci in the zeste-white region of the Drosophila melanogaster X chromosome are expressed both maternally and zygotically has been tested. Maternal gene activity was varied by altering gene dose, and zygotic gene activity was manipulated by use of position-effect variegation of a duplication. Viability is affected when both maternal and zygotic gene activity are reduced, but not when either maternal or zygotic gene activity is normal. Tests of a set of overlapping deficiencies demonstrate that at least three sections of the zeste-white region yield maternal zygotic lethal interactions. Single-cistron mutations at two loci in one of these segments have been tested, and maternal heterozygosity for mutations at both loci give lethal responses of mutant-duplication zygotes. Thus, at least four of the 13 essential functions coded in the zeste-white region are active both maternally and zygotically, suggesting that a substantial fraction of the genome may function at both stages. The normal survival of zygotes when either maternal gene expression or zygotic gene expression is normal, and their inviability when both are depressed, suggests that a developmental stage exists when maternally determined functions and zygotically coded functions are both in use.

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Mutational Analysis of a Histone Deacetylase in Drosophila melanogaster: Missense Mutations Suppress Gene Silencing Associated With Position Effect Variegation

Genetics ◽

10.1093/genetics/154.2.657 ◽

2000 ◽

Vol 154 (2) ◽

pp. 657-668 ◽

Cited By ~ 2

Author(s):

Randy Mottus ◽

Richard E Sobel ◽

Thomas A Grigliatti

Keyword(s):

Drosophila Melanogaster ◽

Histone Deacetylase ◽

Transcriptional Activity ◽

Mutational Analysis ◽

Position Effect ◽

Transcriptional Regulator ◽

Position Effect Variegation ◽

Missense Mutations ◽

Effect Variegation ◽

New Mutations

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.

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Competition Between Different Variegating Rearrangements for Limited Heterochromatic Factors in Drosophila melanogaster

Genetics ◽

10.1093/genetics/145.4.945 ◽

1997 ◽

Vol 145 (4) ◽

pp. 945-959

Author(s):

Vett K Lloyd ◽

Donald A Sinclair ◽

Thomas A Grigliatti

Keyword(s):

Drosophila Melanogaster ◽

Chromosome Rearrangement ◽

Position Effect ◽

Position Effect Variegation ◽

Euchromatic Region ◽

Single Chromosome ◽

Mosaic Expression ◽

Effect Variegation ◽

Protein Components

Position effect variegation (PEV) results from the juxtaposition of a euchromatic gene to heterochromatin. In its new position the gene is inactivated in some cells and not in others. This mosaic expression is consistent with variability in the spread of heterochromatin from cell to cell. As many components of heterochromatin are likely to be produced in limited amounts, the spread of heterochromatin into a normally euchromatic region should be accompanied by a concomitant loss or redistribution of the protein components from other heterochromatic regions. We have shown that this is the case by simultaneously monitoring variegation of a euchromatic and a heterochromatic gene associated with a single chromosome rearrangement. Secondly, if several heterochromatic regions of the genome share limited components of heterochromatin, then some variegating rearrangements should compete for these components. We have examined this hypothesis by testing flies with combinations of two or more different variegating rearrangements. Of the nine combinations of pairs of variegating rearrangements we studied, seven showed nonreciprocal interactions. These results imply that many components of heterochromatin are both shared and present in limited amounts and that they can transfer between chromosomal sites. Consequently, even nonvariegation portions of the genome will be disrupted by re-allocation of heterochromatic proteins associated with PEV. These results have implications for models of PEV.

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