TY - JOUR
T1 - The double-strand break landscape of meiotic chromosomes is shaped by the Paf1 transcription elongation complex in Saccharomyces cerevisiae
AU - Gothwal, Santosh K.
AU - Patel, Neem J.
AU - Colletti, Meaghan M.
AU - Sasanuma, Hiroyuki
AU - Shinohara, Miki
AU - Hochwagen, Andreas
AU - Shinohara, Akira
N1 - Funding Information:
We thank Doug Bishop, Susan Gasser, and Neil Hunter for discussions. We are also indebted to members of the Shinohara lab, especially Hisako Matsumoto and Ayaka Tokumura for their technical assistance. This work was supported by the Japanese Society for the Promotion of Science (JSPS) KAKENHI grants 22125001 and 22125002 to A.S., as well as by grants from the Takeda Science Foundation to A.S. M.S. was supported by JSPS through the Next Generation World-Leading Researchers program. This work was also supported in part by National Institutes of Health grant GM088248 and March Dimes research grant 6-FY13-105 to A.H. S.G. was supported by the Indian government as well as by the Institute for Protein Research. S.K.G., H.S., M.S., A.H., and A.S. conceived and designed the experiments; S.K.G., H.S., and M.S. performed the experiments; S.K.G., M.S., and A.S. analyzed the data; N.J.P. and M.M.C. carried out the microarray experiments and analyzed the data; and S.K.G., M.S., N.J.P., A.H., and A.S. wrote the manuscript.
Publisher Copyright:
© 2016 by the Genetics Society of America.
PY - 2016/2
Y1 - 2016/2
N2 - Histone modification is a critical determinant of the frequency and location of meiotic double-strand breaks (DSBs), and thus recombination. Set1-dependent histone H3K4 methylation and Dot1-dependent H3K79 methylation play important roles in this process in budding yeast. Given that the RNA polymerase II associated factor 1 complex, Paf1C, promotes both types of methylation, we addressed the role of the Paf1C component, Rtf1, in the regulation of meiotic DSB formation. Similar to a set1 mutation, disruption of RTF1 decreased the occurrence of DSBs in the genome. However, the rtf1 set1 double mutant exhibited a larger reduction in the levels of DSBs than either of the single mutants, indicating independent contributions of Rtf1 and Set1 to DSB formation. Importantly, the distribution of DSBs along chromosomes in the rtf1 mutant changed in a manner that was different from the distributions observed in both set1 and set1 dot1 mutants, including enhanced DSB formation at some DSB-cold regions that are occupied by nucleosomes in wild-type cells. These observations suggest that Rtf1, and by extension the Paf1C, modulate the genomic DSB landscape independently of H3K4 methylation.
AB - Histone modification is a critical determinant of the frequency and location of meiotic double-strand breaks (DSBs), and thus recombination. Set1-dependent histone H3K4 methylation and Dot1-dependent H3K79 methylation play important roles in this process in budding yeast. Given that the RNA polymerase II associated factor 1 complex, Paf1C, promotes both types of methylation, we addressed the role of the Paf1C component, Rtf1, in the regulation of meiotic DSB formation. Similar to a set1 mutation, disruption of RTF1 decreased the occurrence of DSBs in the genome. However, the rtf1 set1 double mutant exhibited a larger reduction in the levels of DSBs than either of the single mutants, indicating independent contributions of Rtf1 and Set1 to DSB formation. Importantly, the distribution of DSBs along chromosomes in the rtf1 mutant changed in a manner that was different from the distributions observed in both set1 and set1 dot1 mutants, including enhanced DSB formation at some DSB-cold regions that are occupied by nucleosomes in wild-type cells. These observations suggest that Rtf1, and by extension the Paf1C, modulate the genomic DSB landscape independently of H3K4 methylation.
KW - Double-strand breaks
KW - H3K4 methylation
KW - Meiosis
KW - PAF
KW - Recombination
KW - Rtf1
UR - http://www.scopus.com/inward/record.url?scp=84979876742&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84979876742&partnerID=8YFLogxK
U2 - 10.1534/genetics.115.177287
DO - 10.1534/genetics.115.177287
M3 - Article
C2 - 26627841
AN - SCOPUS:84979876742
VL - 202
SP - 497
EP - 512
JO - Genetics
JF - Genetics
SN - 0016-6731
IS - 2
ER -