Euchromatin factors HULC and Set1C affect heterochromatin organization and mating-type switching in fission yeast Schizosaccharomyces pombe

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

Dokumenter

  • Fulltext

    Forlagets udgivne version, 665 KB, PDF-dokument

  • Alfredo Esquivel-Chávez
  • Takahisa Maki
  • Hideo Tsubouchi
  • Testuya Handa
  • Hiroshi Kimura
  • James E. Haber
  • Thon, Genevieve
  • Hiroshi Iwasaki
Mating-type (P or M) of fission yeast Schizosaccharomyces pombe is determined by the transcriptionally active mat1 cassette and is switched by gene conversion using a donor, either mat2 or mat3, located in an adjacent heterochromatin region (mating-type switching; MTS). In the switching process, heterochromatic donors of genetic information are selected based on the P or M cell type and on the action of two recombination enhancers, SRE2 promoting the use of mat2-P and SRE3 promoting the use of mat3-M, leading to replacement of the content of the expressed mat1 cassette. Recently, we found that the histone H3K4 methyltransferase complex Set1C participates in donor selection, raising the question of how a complex best known for its effects in euchromatin controls recombination in heterochromatin. Here, we report that the histone H2BK119 ubiquitin ligase complex HULC functions with Set1C in MTS, as mutants in the shf1, brl1, brl2 and rad6 genes showed defects similar to Set1C mutants and belonged to the same epistasis group as set1Δ. Moreover, using H3K4R and H2BK119R histone mutants and a Set1-Y897A catalytic mutant, we found that ubiquitylation of histone H2BK119 by HULC and methylation of histone H3K4 by Set1C are functionally coupled in MTS. Cell-type biases in MTS in these mutants suggested that HULC and Set1C inhibit the use of the SRE3 recombination enhancer in M cells, thus favoring SRE2 and mat2-P. Consistent with this, imbalanced switching in the mutants was traced to compromised association of the directionality factor Swi6 with the recombination enhancers in M cells. Based on their known effects at other chromosomal locations, we speculate that HULC and Set1C control nucleosome mobility and strand invasion near the SRE elements. In addition, we uncovered distinct effects of HULC and Set1C on histone H3K9 methylation and gene silencing, consistent with additional functions in the heterochromatic domain.
OriginalsprogEngelsk
TidsskriftGenes and Genetic Systems
Vol/bind97
Udgave nummer3
Sider (fra-til)123-138
Antal sider16
ISSN1341-7568
DOI
StatusUdgivet - 2022

Bibliografisk note

Funding Information:
We acknowledge the following grant support: Grants-in-Aid for Scientific Research (A) (JP18H03985) to H. I., for Scientific Research (B) (JP18H02371) to H. T. and for Scientific Research on Innovative Areas (JP18H05527) to H. K. from the Japan Society for the Promotion of Science (JSPS); grant R35 GM127029 to J. E. H. from NIH; the World Research Hub Initiative (WHRI) program at the Tokyo Institute of Technology to J. E. H.; grant R167-A11089 to G. T. from the Danish Cancer Research Society; and the Otsuka Toshimi Scholarship Foundation to A. E.-C.

Publisher Copyright:
© 2022 The Author(s).

ID: 333436193