Molecular cloning and chromosomal localization of a novel <i>Drosophila</i> protein phosphatase

Variegated phenotypes often result from chromosomal rearrangements that place euchromatic genes next to heterochromatin. In such rearrangements, the condensed structure of heterochromatin can spread into euchromatic regions, which then assume the morphology of heterochromatin and become transcriptionally inactive. In position-effect variegation (PEV) therefore, gene inactivation results from a change in chromatin structure. PEV has been intensively investigated in the fruitfly Drosophila, where the phenomenon allows a genetic dissection of chromatin components. Consequently, many genes have been identified which, when mutated, act as dominant modifiers (suppressors or enhancers) of PEV. Data available already demonstrate that genetic, molecular and developmental analysis of these genes provides an avenue to the identification of regulatory and structural chromatin components, and hence to fundamental aspects of chromosome structure and function.

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“…For instance, Suvnr(3)6 at X7B on the third chromosome encodes a protein phosphatase (PP1) (ref. 40 and Baksa et ~1 . in preparation).…”

Section: Pev Modifiers and Chromatin Genesmentioning

confidence: 94%

Position effect variegation and chromatin proteins

1992

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“…Methylated Lys-9 on histone H3 creates a binding site for HP1 proteins in yeast and mammals (6)(7)(8). Su(var)2-4 and Su(var)3-6 are strong dominant suppressors of PEV, although the mechanisms of these suppressors are unknown (16,21). Su(var)3-6 encodes a protein phosphatase (21) that might be essential for modification of chromosomal proteins such as Su(var) 3-7 (22).…”

Section: Several Other Modifiers Of Pev Have Been Reported Includingmentioning

confidence: 99%

Transcriptional repression of euchromatic genes by Drosophila heterochromatin protein 1 and histone modifiers

Hwang

Eissenberg

Worman

2001

Proc. Natl. Acad. Sci. U.S.A.

110

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In Drosophila, heterochromatin protein 1 (HP1) suppresses the expression of euchromatic genes that are artificially translocated adjacent to heterochromatin by expanding heterochromatin structure into neighboring euchromatin. The purpose of this study was to determine whether HP1 functions as a transcriptional repressor in the absence of chromosome rearrangements. Here, we show that Drosophila HP1 normally represses the expression of four euchromatic genes in a dosage-dependent manner. Three genes regulated by HP1 map to cytological region 31 of chromosome 2, which is immunostained by anti-HP1 antibodies in the salivary gland. The repressive effect of HP1 is decreased by mutation in Su(var)3-9, whose mammalian orthologue encodes a histone H3 methyltransferase and mutation in Su(var)2-1, which is correlated with histone H4 deacetylation. These data provide genetic evidence that an HP1-family protein represses the expression of euchromatic genes in a metazoan, and that histone modifiers cooperate with HP1 in euchromatic gene repression.H eterochromatin protein 1 (HP1) first was identified as a component of heterochromatin in Drosophila polytene chromosomes (1). Subsequently, it was shown to mediate variegated silencing of euchromatic genes that are placed abnormally next to constitutive heterochromatin, a phenomenon known as position-effect variegation (PEV; refs. 2-4). In contrast to its role in suppressing genes that are localized abnormally on chromosomes, the only documented role of HP1 in normal gene regulation is in the activation of two Drosophila heterochromatic genes, light and rolled (5).HP1-family proteins bind to histones and DNA (6-9). Lys-9 of histone H3 is methylated by the modifier proteins SUV39H1 and Suv39H1, the human and murine orthologues of the Drosophila Su(var)3-9 gene product, respectively (10, 11). Histone H3 methylation is thought to promote transcriptional silencing by creating a binding site for HP1-family proteins to form heterochromatic subdomains (6-8). Histone deacetylation also is thought to promote silencing. Mutations in the Drosophila histone deacetylase (HDAC) 1 suppress PEV, indicating that HDAC1 normally promotes silencing (12). Similarly, Su(var)2-1 mutations suppress PEV silencing and cause hyperacetylation of histones (13).Although HP1 is involved in heterochromatin structure and position-effect silencing, there are no examples of normal transcriptional repression of genes by HP1. Among HP1-family proteins, only Swi6p in fission yeast has been shown to be involved in normal gene repression, silencing the mating type cassettes (14, 15). Here, we describe a previously unreported role for HP1 in the repression of euchromatic genes in Drosophila. We have identified genes residing in the euchromatin of chromosome 2 that are repressed normally by HP1 and other heterochromatin-associated factors. In contrast to previous examples of euchromatic gene silencing by heterochromatin, these HP1-repressed genes are located well away from constitutive heterochromatin. The genes show a gr...

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“…Genetic and cytological mapping located thr to the interval 54F-55A between the proximal breakpoints of Df(2R)Pcl1lB and Df(2R)PclW5 (Tearle, personal communication; Saint, unpublished data). This placed thr between the grainyhead (grh) locus (Bray and Kafatos, 1991) and the protein phosphatase Y gene (Dombradi et al, 1989) (D'Andrea and Saint, unpublished observations).…”

Section: Vol 4 November 1993mentioning

confidence: 99%

The three rows gene of Drosophila melanogaster encodes a novel protein that is required for chromosome disjunction during mitosis.

D’Andrea

Stratmann

Lehner

et al. 1993

MBoC

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Zygotic expression of the three rows (thr) gene of Drosophila melanogaster is required for normal cell proliferation during embryogenesis. Mitotic defects in thr mutant embryos begin during mitosis 15, and all subsequent divisions are disrupted. Chromosome disjunction and consequently cytokinesis fail during these defective mitoses, although the initial mitotic processes (chromosome condensation, spindle assembly, metaphase plate formation, and cyclin degradation) are not affected. Despite the failure of chromosome disjunction and cytokinesis, later mitotic events (chromosome decondensation) and subsequent cell cycle progression continue. The thr gene has been isolated and shown to encode a 1209 amino acid protein that shares no extended sequence similarity with known proteins. thr mRNA is present as maternal mRNA that degrades at the time of cellularization. At this and all subsequent times during embryogenesis, zygotic expression correlates with mitotic proliferation. These observations, together with the observation that the zygotic phenotype of thr mutant embryos is influenced by the maternal genotype, suggest that the embryonic phenotype results from exhaustion of the maternal thr contribution and does not reflect a developmentally restricted requirement for thr function. Our results indicate that the novel thr product is required specifically for chromosome disjunction during all mitoses.

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Molecular cloning and chromosomal localization of a novel Drosophila protein phosphatase

Cited by 37 publications

References 22 publications

Position effect variegation and chromatin proteins

Position effect variegation and chromatin proteins

Transcriptional repression of euchromatic genes by Drosophila heterochromatin protein 1 and histone modifiers

The three rows gene of Drosophila melanogaster encodes a novel protein that is required for chromosome disjunction during mitosis.

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