The genetics of position — effect variegation modifying loci inDrosophila melanogaster

Wustmann, G.; Szidonya, János; Taubert, Heike; Reuter, Günter

doi:10.1007/bf02464926

Cited by 171 publications

(100 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Therefore, the substrate specificity is likely caused by minor differences in the amino acid sequences of CDs from different proteins. The connection between Suv39h1 and HP1 is consistent with Drosophila research showing that the genes encoding HP1 and SU(VAR)3-9 genetically interact with the heterochromatin silencing system (8) and that the proteins physically interact (42). The relationship between HP1 and Suv39h1 has been maintained by the S. pombe homologues, Swi6 and Clr4, respectively (43,44), suggesting evolutionary conservation in this mechanism of chromosome association and heterochromatic gene silencing.…”

Section: Hp1 Follows Codesupporting

confidence: 83%

“…1A). Consistent with this localization, the gene encoding HP1, Su(var) [2][3][4][5], was isolated as a dominant suppressor of position effect variegation (PEV) (8,9). PEV is the mosaic pattern of expression exhibited by genes placed near centric heterochromatin by chromosomal rearrangements or transposition events (10).…”

mentioning

confidence: 83%

“…The gene encoding HP1, Su(var)2-5, was isolated in a screen for suppressors and enhancers of PEV of the white ϩ gene brought into juxtaposition with heterochromatin through a chromosomal rearrangement (8). To determine the effects of HP1 on chromatin packaging, stocks containing the well-characterized Drosophila hsp26 gene inserted within centric heterochromatin were used for chromatin structure analysis (16).…”

Section: Hp1 Regulates Gene Expressionmentioning

confidence: 99%

See 2 more Smart Citations

Does heterochromatin protein 1 always follow code?

Kirschmann

Wallrath

2002

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

172

175

View full text Add to dashboard Cite

Heterochromatin protein 1 (HP1) is a conserved chromosomal protein that participates in chromatin packaging and gene silencing. A loss of HP1 leads to lethality in Drosophila and correlates with metastasis in human breast cancer cells. On Drosophila polytene chromosomes HP1 is localized to centric regions, telomeric regions, in a banded pattern along the fourth chromosome, and at many sites scattered throughout the euchromatic arms. Recently, one mechanism of HP1 chromosome association was revealed; the amino-terminal chromo domain of HP1 interacts with methylated lysine nine of histone H3, consistent with the histone code hypothesis. Compelling data support this mechanism of HP1 association at centric regions. Is this the only mechanism by which HP1 associates with chromosomes? Interest is now shifting toward the role of HP1 within euchromatic domains. Accumulating evidence in Drosophila and mammals suggests that HP1 associates with chromosomes through interactions with nonhistone chromosomal proteins at locations other than centric heterochromatin. Does HP1 play a similar role in chromatin packaging and gene regulation at these sites as it does in centric heterochromatin? Does HP1 associate with the same proteins at these sites as it does in centric heterochromatin? A first step toward answering these questions is the identification of sequences associated with HP1 within euchromatic domains. Such sequences are likely to include HP1 ''target genes'' whose discovery will aid in our understanding of HP1 lethality in Drosophila and metastasis of breast cancer cells.

show abstract

Section: Hp1 Follows Codesupporting

confidence: 83%

mentioning

confidence: 83%

Section: Hp1 Regulates Gene Expressionmentioning

confidence: 99%

See 1 more Smart Citation

Does heterochromatin protein 1 always follow code?

Kirschmann

Wallrath

2002

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

172

175

View full text Add to dashboard Cite

show abstract

“…Most strikingly, the closest homologue of PIASy in Drosophila, Su(var)2-10, encodes an essential protein (Hari et al, 2001). Su(var)2-10 was initially identified as a Suppressor of Position-Effect Variegation (Wustmann et al, 1989). Mutations in this gene cause both minichromosome and endogenous chromosome inheritance defects (Hari et al, 2001): Su(var)2-10 mutants show aberrant condensation of mitotic chromosomes, as well as faulty chromosome organization within interphase nuclei, leading to the proposal that Su(var)2-10 controls multiple aspects of chromosome structure and function throughout the cell cycle.…”

Section: + C O N T R O L I G G + a N T I -P I A S Y -C + A N T I -P Imentioning

confidence: 99%

PIASy mediates SUMO-2 conjugation of Topoisomerase-II on mitotic chromosomes

Azuma

Arnaoutov

Anan

et al. 2005

EMBO J

136

173

View full text Add to dashboard Cite

Here we show that the PIASy protein is specifically required for mitotic modification of Topoisomerase-II by SUMO-2 conjugation in Xenopus egg extracts. PIASy was unique among the PIAS family members in its capacity to bind mitotic chromosomes and recruit Ubc9 onto chromatin. These properties were essential, since PIASy mutants that did not bind chromatin or failed to recruit Ubc9 were functionally inactive. We observed that PIASy depletion eliminated essentially all chromosomal accumulation of EGFP-SUMO-2-conjugated species, suggesting that it is the primary E3-like factor for mitotic chromosomal substrates of SUMO-2. PIASy-dependent SUMO-2-conjugated species were highly concentrated on the inner centromere, and inhibition of PIASy blocked anaphase sister chromatid segregation in egg extracts. Taken together, our observations suggest that PIASy is a critical regulator of mitotic SUMO-2 conjugation for Topoisomerase-II and other chromosomal substrates, and that its activity may have particular relevance for centromeric functions required for proper chromosome segregation.

show abstract

“…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

View full text Add to dashboard Cite

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...

show abstract

The genetics of position — effect variegation modifying loci inDrosophila melanogaster

Cited by 171 publications

References 23 publications

Does heterochromatin protein 1 always follow code?

Does heterochromatin protein 1 always follow code?

PIASy mediates SUMO-2 conjugation of Topoisomerase-II on mitotic chromosomes

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

Contact Info

Product

Resources

About