Quantitative Methods to Investigate the 4D Dynamics of Heterochromatic Repair Sites in Drosophila Cells
Christopher P. CaridiLætitia DelabaereHarianto TjongH. Esteban HoppDevika DasFrank AlberIrene Chiolo
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Heterochromatin protein 1
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Significance Eukaryotic chromosomes are organized into specialized, nucleoprotein domains that can regulate nuclear functions. Heterochromatin is a silenced chromatin region essential for maintaining genomic stability and driving developmental processes. Cell biological studies have indicated that heterochromatin is highly condensed, though the complicated structure and dynamics of heterochromatin have rendered it difficult to characterize. Here we reconstitute heterochromatin fibers with purified components and exploit a powerful combination of sedimentation velocity, molecular modeling, and atomic force microscopy to characterize the stoichiometry and condensed conformation of heterochromatin fibers.
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The transcriptional silencing of the cryptic mating-type loci in Saccharomyces cerevisiae is one of the best-studied models of repressive heterochromatin. However, this type of heterochromatin, which is mediated by the Sir proteins, has a distinct molecular composition compared to the more ubiquitous type of heterochromatin found in Schizosaccharomyces pombe, other fungi, animals, and plants and characterized by the presence of HP1 (heterochromatin protein 1). This review discusses how the loss of important heterochromatin proteins, including HP1, in the budding yeast lineage presented an evolutionary opportunity for the development and diversification of alternative varieties of heterochromatin, in which the conserved deacetylase Sir2 and the replication protein Orc1 play key roles. In addition, we highlight how this diversification has been facilitated by gene duplications and has contributed to adaptations in lifestyle.
Heterochromatin protein 1
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Schizosaccharomyces
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Subtelomere
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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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Heterochromatin protein 1
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Heterochromatin plays important roles in eukaryotic genome regulation. However, the repressive nature of heterochromatin combined with its propensity to self-propagate necessitates robust mechanisms to contain heterochromatin within defined boundaries and thus prevent silencing of expressed genes. Here we show that loss of the PAF complex (PAFc) component Leo1 compromises chromatin boundaries, resulting in invasion of heterochromatin into flanking euchromatin domains. Similar effects are seen upon deletion of other PAFc components, but not other factors with related functions in transcription-associated chromatin modification, indicating a specific role for PAFc in heterochromatin regulation. Loss of Leo1 results in reduced levels of H4K16 acetylation at boundary regions, while tethering of the H4K16 acetyltransferase Mst1 to boundary chromatin suppresses heterochromatin spreading in leo1Δ cells, suggesting that Leo1 antagonises heterochromatin spreading by promoting H4K16 acetylation. Our findings reveal a previously undescribed role for PAFc in regulating global heterochromatin distribution.
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Euchromatin
Heterochromatin protein 1
Acridine orange
Constitutive heterochromatin
Developmental Biology
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Abstract Budding yeast Saccharomyces cerevisiae and fission yeast Schizosaccharomyces pombe are good models for heterochromatin study. In S. pombe , H3K9 methylation and Swi6, an ortholog of mammalian HP1, lead to heterochromatin formation. However, S. cerevisiae does not have known epigenetic silencing markers and instead has Sir proteins to regulate silent chromatin formation. Although S. cerevisiae and S. pombe form and maintain heterochromatin via mechanisms that appear to be fundamentally different, they share important common features in the heterochromatin structural proteins. Heterochromatin loci are localized at the nuclear periphery by binding to perinuclear membrane proteins, thereby producing distinct heterochromatin foci, which sequester heterochromatin structural proteins. In this review, we discuss the nuclear peripheral anchoring of heterochromatin foci and its functional relevance to heterochromatin formation and maintenance. Graphical Abstract
Heterochromatin protein 1
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Atypical heterochromatin forms on telomeres and correlates with ALT activities.
Heterochromatin protein 1
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