Chromatin-associated genes protect the yeast genome from Ty1 insertional mutagenesis.
Chromosomal genes modulate Ty retrotransposon movement in the genome of Saccharomyces cerevisiae. We have screened a collection of 4739 deletion mutants to identify those that increase Ty1 mobility (Ty1 restriction genes). Among the 91 identified mutants, 80% encode products involved in nuclear processes such as chromatin structure and function, DNA repair and recombination, and transcription. However, bioinformatic analyses encompassing additional Ty1 and Ty3 screens indicate that 264 unique genes involved in a variety of biological processes affect Ty mobility in yeast. Further characterization of 33 of the mutants identified here show that Ty1 RNA levels increase in 5 mutants and the rest affect mobility post-transcriptionally. RNA and cDNA levels remain unchanged in mutants defective in transcription elongation, including ckb2Delta and elf1Delta, suggesting that Ty1 integration may be more efficient in these strains. Insertion-site preference at the CAN1 locus requires Ty1 restriction genes involved in histone H2B ubiquitination by Paf complex subunit genes, as well as BRE1 and RAD6, histone H3 acetylation by RTT109 and ASF1, and transcription elongation by SPT5. Our results indicate that multiple pathways restrict Ty1 mobility and histone modifications may protect coding regions from insertional mutagenesis.
Nyswaner
Katherine M
KM
Gene Regulation and Chromosome Biology Laboratory, Center for Cancer Research, Science Applications International Corporation, National Cancer Institute, Frederick, Maryland 21702-1201, USA.
Checkley
Mary Ann
MA
Yi
Ming
M
Stephens
Robert M
RM
Garfinkel
David J
DJ
D002843:Chromatin / Q000235:genetics*; D019295:Computational Biology; D018076:DNA, Complementary / Q000235:genetics; D017353:Gene Deletion; D005800:Genes, Fungal; D008957:Models, Genetic; D016254:Mutagenesis, Insertional / Q000235:genetics*; D018626:Retroelements / Q000235:genetics*; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D054875:Ubiquitination
D002843:Chromatin; D018076:DNA, Complementary; D018626:Retroelements; D029701:Saccharomyces cerevisiae Proteins