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Mutations in deoxyribonucleotide biosynthesis pathway cause spreading of silencing across heterochromatic barriers at the mating‐type region of the fission yeast
Author(s) -
Singh Gurjeet,
Klar Amar J. S.
Publication year - 2008
Publication title -
yeast
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.923
H-Index - 102
eISSN - 1097-0061
pISSN - 0749-503X
DOI - 10.1002/yea.1569
Subject(s) - biology , heterochromatin , genetics , heterochromatin protein 1 , schizosaccharomyces pombe , gene silencing , schizosaccharomyces , mating of yeast , histone , chromatin , gene , mutant
The mat2,3 ‐region of Schizosaccharomyces pombe is flanked by two inverted repeat elements, IRL and IRR , which define the boundaries of the silent domain resulting from heterochromatin assembly in the region. We employed a genetic screen to isolate factors whose mutations allowed spreading of heterochromatin across boundary elements. Surprisingly, this screen revealed that mutations in the genes required for deoxyribonucleotide biosynthesis, cdc22 (encoding the large subunit of ribonucleotide reductase) and tds1 (putative thymidylate synthase), cause silencing of marker genes inserted outside of the silent domain. Chromatin‐immunoprecipitation analysis showed that histone H3 lysine 9 methylation modification, an epigenetic mark associated with gene silencing, is enriched by two‐ to three‐fold in the cdc22 mutant as compared to the level found in the wild‐type strain in regions outside the silent domain. The spreading of heterochromatin across barriers required functional Atf1/Pcr1, ATF‐CREB family proteins, but not the RNA‐interference Dcr1, Ago1, or Rdp1 factors, previously implicated in silencing. These results implicate the deoxyribonucleotide biosynthesis pathway in limiting epigenetic controls at barrier elements at the mating‐type region, but the mechanism remains unknown. Published in 2007 by John Wiley & Sons, Ltd.