Integrity of a heterochromatic domain ensured by its boundary elements
| Autor: | Sebastian Jespersen Charlton, Maria Louise Mønster Jørgensen, Geneviève Thon |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Chromosomal Proteins
Non-Histone Heterochromatin Inverted repeat Mutant Cell Cycle Proteins Chromatin boundaries Methylation Histones gene silencing Transcription Factors TFIII RNA interference Schizosaccharomyces Genetics single-cell studies Nucleosome Epigenetics Cell Nucleus Multidisciplinary Single-cell studies biology Chemistry Inverted Repeat Sequences heterochromatin Gene silencing Nuclear Proteins Biological Sciences Fission yeast fission yeast chromatin boundaries Cell biology DNA-Binding Proteins Histone biology.protein RNA Interference Schizosaccharomyces pombe Proteins Rix1 complex |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America Charlton, S J, Jørgensen, M M & Thon, G 2020, ' Integrity of a heterochromatic domain ensured by its boundary elements ', Proceedings of the National Academy of Sciences of the United States of America, vol. 117, no. 35, pp. 21504-21511 . https://doi.org/10.1073/pnas.2010062117 |
| ISSN: | 1091-6490 0027-8424 |
| Popis: | Significance The fission yeast silent mating-type region provides an excellent system to ask how chromatic domains with opposite effects on gene expression coexist side by side along chromosomes and to investigate roles played by DNA elements and architectural proteins in the phenomenon. By showing that the IR-L and IR-R chromatin boundaries favor heterochromatin formation in the domain that separates them, dependent on each other and on binding sites for the architectural factor TFIIIC, our work brings to light an important function of these elements and supports the notion that similar types of interactions between boundaries might in other organisms as well stimulate heterochromatin formation in intervening chromosomal loops to actively shape gene expression landscapes. In fission yeast, the inverted repeats IR-L and IR-R function as boundary elements at the edges of a 20-kb silent heterochromatic domain where nucleosomes are methylated at histone H3K9. Each repeat contains a series of B-box motifs physically associated with the architectural TFIIIC complex and with other factors including the replication regulator Sap1 and the Rix1 complex (RIXC). We demonstrate here the activity of these repeats in heterochromatin formation and maintenance. Deletion of the entire IR-R repeat or, to a lesser degree, deletion of just the B boxes impaired the de novo establishment of the heterochromatic domain. Nucleation proceeded normally at the RNA interference (RNAi)-dependent element cenH but subsequent propagation to the rest of the region occurred at reduced rates in the mutants. Once established, heterochromatin was unstable in the mutants. These defects resulted in bistable populations of cells occupying alternate “on” and “off” epigenetic states. Deleting IR-L in combination with IR-R synergistically tipped the balance toward the derepressed state, revealing a concerted action of the two boundaries at a distance. The nuclear rim protein Amo1 has been proposed to tether the mating-type region and its boundaries to the nuclear envelope, where Amo1 mutants displayed milder phenotypes than boundary mutants. Thus, the boundaries might facilitate heterochromatin propagation and maintenance in ways other than just through Amo1, perhaps by constraining a looped domain through pairing. |
| Databáze: | OpenAIRE |
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