Yin and Yang of histone H2B roles in silencing and longevity: a tale of two arginines.
In budding yeast, silent chromatin is defined at the region of telomeres, rDNA loci, and silent mating loci. Although the silent chromatin at different loci shows structural similarity, the underlying mechanism to establish, maintain, and inherit these structures may be fundamentally different. In this study, we found two arginine residues within histone H2B, which are specifically required to maintain either the telomeric or the rDNA silenct chromatin. Arginine 95 (R95) plays a specific role at telomeres, whereas arginine 102 (R102) is required to maintain the silent chromatin at rDNA and to ensure the integrity of rDNA loci by suppressing recombination between rDNA repeats. R95 mutants show enhanced rDNA silencing but a paradoxically low Sir2 protein abundance. Furthermore weakened silencing at telomeres in R95 mutants can be suppressed by a specific SIR3 allele, SIR3-D205N, which increases the affinity of Sir proteins to telomeres, suggesting H2B-R95 may directly mediate telomeric Sir protein-nucleosome interactions. Double mutations of R95 and R102 lead to desilencing of both rDNA and telomeres, indicating both arginines are necessary to ensure integrity of silent chromatin at these loci. Furthermore, mutations of R102 cause accumulation of extrachromosomal rDNA circles and reduce life span, suggesting that histone H2B contributes to longevity.
Dai
Junbiao
J
High Throughput Biology Center, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Hyland
Edel M
EM
Norris
Anne
A
Boeke
Jef D
JD
D000483:Alleles; D019943:Amino Acid Substitution / Q000235:genetics; D001120:Arginine / Q000235:genetics / Q000378:metabolism*; D004261:DNA Replication / Q000235:genetics; D004275:DNA, Ribosomal / Q000235:genetics; D015966:Gene Expression Regulation, Fungal; D020868:Gene Silencing; D016153:Genes, Suppressor; D056426:Genetic Loci / Q000235:genetics; D006657:Histones / Q000378:metabolism*; D008957:Models, Genetic; D008958:Models, Molecular; D009154:Mutation / Q000235:genetics; D009707:Nucleosomes / Q000378:metabolism; D010641:Phenotype; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D056565:Sirtuin 2 / Q000235:genetics / Q000378:metabolism; D013489:Suppression, Genetic; D016615:Telomere / Q000235:genetics; D013997:Time Factors; D014158:Transcription, Genetic; D016709:Yin-Yang
D004275:DNA, Ribosomal; D006657:Histones; D009707:Nucleosomes; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae; D001120:Arginine; C087778:SIR2 protein, S cerevisiae; D056565:Sirtuin 2