A heat shock-activated cDNA rescues the recessive lethality of mutations in the heterochromatin-associated protein HP1 of Drosophila melanogaster

Eissenberg, Joel C.; Hartnett, Thomas

doi:10.1007/bf00280383

Cited by 45 publications

(15 citation statements)

References 23 publications

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“…The introduction of Hsp7O-lacZ as a PEV marker has allowed us to show that heterochromatic silencing begins early in embryogenesis shortly after the appearance of heterochromatin in late syncytial blastoderm (James et al, 1989). This finding is consistent with studies showing that silencing of a variegating locus can be modified either by altering the rearing temperature or changing the dosage of a PEV modifier during embryogenesis (Hartmann-Goldstein, 1967;Eissenberg and Hartnett, 1993).…”

Section: Discussionsupporting

confidence: 92%

“…Thus, silencing in 'large patch' variegation is assumed to occur as early as blastoderm because of a coincident temperaturesensitive period (Chen, 1948;Hartmann-Goldstein, 1967;Spofford, 1976), and fine-grained mosaicism is explained by a later temperature-sensitive period spanning the pupal stage (Spofford, 1976;Tartof and Bremer, 1990). In contrast to these discrete periods, a study based on dosage alteration of a heterochromatin-associated protein has suggested that variegation can be modified at any time within a continuous interval from blastoderm to late larval development (Eissenberg and Hartnett, 1993). Alternatively, another method to deduce the timing of variegated silencing is to determine how early in development variegated expression can be observed, and, by using PEV markers that can be expressed prior to adulthood, mosaic larval tissues have been reported (Spofford, 1976;Kornher and Kauffman, 1986;Spradling 1993).…”

Section: Introductionmentioning

confidence: 99%

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Developmental timing and tissue specificity of heterochromatin-mediated silencing.

Bishop

Eissenberg

1996

The EMBO Journal

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Heterochromatic position‐effect variegation (PEV) describes the mosaic phenotype of a euchromatic gene placed next to heterochromatin. Heterochromatin‐mediated silencing has been studied extensively in Drosophila, but the lack of a ubiquitous reporter gene detectable at any stage has prevented a direct developmental characterization of this phenomenon. Current models attribute variegation to the establishment of a heritable silent state in a subset of the cells and invoke differences in the timing of silencing to explain differences in the patch size of various mosaic patterns. In order to follow the course of heterochromatic silencing directly, we have generated Drosophila lines variegating for a lacZ reporter that can be induced in virtually all cells at any developmental stage. Our data indicate that silencing begins in embryogenesis and persists in both somatic and germline lineages. A heterogeneity in the extent of silencing is also revealed; silencing is suppressed in differentiated tissues but remains widespread in larval imaginal discs containing precursor cells for adult structures. Using eye development as an example, we propose that the mosaic phenotype is determined during differentiation by a variegated relaxation in heterochromatic silencing. Though unpredicted by prevailing models, this mechanism is evident in other analogous systems.

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Developmental timing and tissue specificity of heterochromatin-mediated silencing.

Bishop

Eissenberg

1996

The EMBO Journal

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“…To test the functional significance of mutant protein binding to heterochromatin, we examined the ability of the different mutations and of the chimeric protein to complement an existing mutation of HP1. Wild-type HP1 cDNA under heat-shock control can support HP1 overexpression and enhance position-effect variegation (Eissenberg et al, 1992;Eissenberg and Hartnett, 1993). An analogous complementation test was performed for each of the mutant HP1 proteins expressed in transgenic animals.…”

Section: Creation Of Chromo Domain Mutations and Intracellular Localimentioning

confidence: 99%

Functional analysis of the chromo domain of HP1.

1995

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Heterochromatin protein 1 (HP1) is a non‐histone chromosomal protein in Drosophila with dosage‐dependent effects on heterochromatin‐mediated gene silencing. An evolutionarily conserved amino acid sequence in the N‐terminal half of HP1 (the ‘chromo domain’) shares > 60% sequence identity with a motif found in the Polycomb protein, a silencer of homeotic genes. We report here that point mutations in the HP1 chromo domain abolish the ability of HP1 to promote gene silencing. We show that the HP1 chromo domain, like the Polycomb chromo domain, has chromosome binding activity, but to distinct chromosomal sites. We constructed a chimeric HP1‐Polycomb protein, consisting of the chromo domain of Polycomb in the context of HP1, and show that it binds to both heterochromatin and Polycomb binding sites in polytene chromosomes. In flies expressing chimeric HP1‐Polycomb protein, endogenous HP1 is mislocalized to Polycomb binding sites, and endogenous polycomb is misdirected to the heterochromatic chromocenter, suggesting that both proteins are recruited to their distinct chromosomal binding sites through protein‐protein contacts. Chimeric HP1‐Polycomb protein expression in transgenic flies promotes heterochromatin‐mediated gene silencing, supporting the view that the chromo domain homology reflects a common mechanistic basis for homeotic and heterochromatic silencing.

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“…However, it remains to be established whether, in vivo, HP1 targeting is a general phenomena or limited to certain tissues. Furthermore, the late larval lethality associated with the Drosophila Su(var)2-5 mutation has precluded studies on the specific function of HP1 in defined developmental processes (Eissenberg and Hartnett, 1993). To gain insight into the function of HP1 proteins throughout development, we have undertaken a genetic analysis of HP1-like proteins from Caenorhabditis elegans.…”

Section: Introductionmentioning

confidence: 99%

A heterochromatin protein 1 homologue in Caenorhabditis elegans acts in germline and vulval development

et al. 2002

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Proteins of the highly conserved heterochromatin protein 1 (HP1) family have been found to function in the dynamic organization of nuclear architecture and in gene regulation throughout the eukaryotic kingdom. In addition to being key players in heterochromatin-mediated gene silencing, HP1 proteins may also contribute to the transcriptional repression of euchromatic genes via the recruitment to specific promoters. To investigate the role played by these different activities in specific developmental pathways, we identified HP1 homologues in the genome of Caenorhabditis elegans and used RNA-mediated interference to study their function. We show that one of the homologues, HPL-2, is required for the formation of a functional germline and for the development of the vulva by acting in an Rb-related pathway. We suggest that, by acting as repressors of gene expression, HP1 proteins may fulfil specific functions in both somatic and germline differentiation processes throughout development.

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A heat shock-activated cDNA rescues the recessive lethality of mutations in the heterochromatin-associated protein HP1 of Drosophila melanogaster

Cited by 45 publications

References 23 publications

Developmental timing and tissue specificity of heterochromatin-mediated silencing.

Developmental timing and tissue specificity of heterochromatin-mediated silencing.

Functional analysis of the chromo domain of HP1.

A heterochromatin protein 1 homologue in Caenorhabditis elegans acts in germline and vulval development

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