Dependency of Heterochromatin Domains on Replication Factors

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  • Author: Jahn, Leonie Johanna

    University of Copenhagen

  • Author: Mason, Bethany

    University of Copenhagen, Denmark

  • Author: Brøgger, Peter

    University of Copenhagen, Denmark

  • Author: Toteva, Tea

    University of Copenhagen, Denmark

  • Author: Nielsen, Dennis Kim

    University of Copenhagen, Denmark

  • Author: Thon, Genevieve

    University of Copenhagen, Denmark

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Chromatin structure regulates both genome expression and dynamics in eukaryotes, where large heterochromatic regions are epigenetically silenced through the methylation of histone H3K9, histone deacetylation, and the assembly of repressive complexes. Previous genetic screens with the fission yeast Schizosaccharomyces pombe have led to the identification of key enzymatic activities and structural constituents of heterochromatin. We report here on additional factors discovered by screening a library of deletion mutants for silencing defects at the edge of a heterochromatic domain bound by its natural boundarythe IR-R+ elementor by ectopic boundaries. We found that several components of the DNA replication progression complex (RPC), including Mrc1/Claspin, Mcl1/Ctf4, Swi1/Timeless, Swi3/Tipin, and the FACT subunit Pob3, are essential for robust heterochromatic silencing, as are the ubiquitin ligase components Pof3 and Def1, which have been implicated in the removal of stalled DNA and RNA polymerases from chromatin. Moreover, the search identified the cohesin release factor Wpl1 and the forkhead protein Fkh2, both likely to function through genome organization, the Ssz1 chaperone, the Fkbp39 proline cis-trans isomerase, which acts on histone H3P30 and P38 in Saccharomyces cerevisiae, and the chromatin remodeler Fft3. In addition to their effects in the mating-type region, to varying extents, these factors take part in heterochromatic silencing in pericentromeric regions and telomeres, revealing for many a general effect in heterochromatin. This list of factors provides precious new clues with which to study the spatiotemporal organization and dynamics of heterochromatic regions in connection with DNA replication.
Original languageEnglish
JournalG3: Genes, Genomes, Genetics (Bethesda)
Volume8
Issue number2
Pages (from-to)477-489
ISSN2160-1836
DOIs
Publication statusPublished - 2018
Externally publishedYes

Bibliographical note

This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/ licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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    Research areas

  • DNA replication, Fission yeast, Gene silencing, Heterochromatin, Chromatin remodeling, Cohesins, Genetic screen, Mating-type region, Nuclear organization, Proline isomerase

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