Chaperone control of the activity and specificity of the histone H3 acetyltransferase Rtt109.
Acetylation of Saccharomyces cerevisiae histone H3 on K56 by the histone acetyltransferase (HAT) Rtt109 is important for repairing replication-associated lesions. Rtt109 purifies from yeast in complex with the histone chaperone Vps75, which stabilizes the HAT in vivo. A whole-genome screen to identify genes whose deletions have synthetic genetic interactions with rtt109Delta suggests Rtt109 has functions in addition to DNA repair. We show that in addition to its known H3-K56 acetylation activity, Rtt109 is also an H3-K9 HAT, and we show that Rtt109 and Gcn5 are the only H3-K9 HATs in vivo. Rtt109's H3-K9 acetylation activity in vitro is enhanced strongly by Vps75. Another histone chaperone, Asf1, and Vps75 are both required for acetylation of lysine 9 on H3 (H3-K9ac) in vivo by Rtt109, whereas H3-K56ac in vivo requires only Asf1. Asf1 also physically interacts with the nuclear Hat1/Hat2/Hif1 complex that acetylates H4-K5 and H4-K12. We suggest Asf1 is capable of assembling into chromatin H3-H4 dimers diacetylated on both H4-K5/12 and H3-K9/56.
Fillingham
Jeffrey
J
Banting and Best Department of Medical Research, Terrence Donnelly Centre for Cellular and Biomolecular Research (CCBR), University of Toronto, 160 College St., Toronto, Ontario M5S 3E1, Canada.
Recht
Judith
J
Silva
Andrea C
AC
Suter
Bernhard
B
Emili
Andrew
A
Stagljar
Igor
I
Krogan
Nevan J
NJ
Allis
C David
CD
Keogh
Michael-Christopher
MC
Greenblatt
Jack F
JF
D000107:Acetylation; D018797:Cell Cycle Proteins / Q000378:metabolism; D002467:Cell Nucleus / Q000201:enzymology; D004249:DNA Damage; D004260:DNA Repair; D004795:Enzyme Stability; D016681:Genome, Fungal; D042822:Genomic Instability; D051548:Histone Acetyltransferases / Q000378:metabolism*; D006657:Histones / Q000378:metabolism*; D008239:Lysine / Q000378:metabolism; D018832:Molecular Chaperones / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D011485:Protein Binding; D016196:S Phase; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000201:enzymology* / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D013379:Substrate Specificity
C109731:ASF1 protein, S cerevisiae; D018797:Cell Cycle Proteins; D006657:Histones; D018832:Molecular Chaperones; D029701:Saccharomyces cerevisiae Proteins; C525548:Vps75 protein, S cerevisiae; D051548:Histone Acetyltransferases; C517120:Rtt109 protein, S cerevisiae; D008239:Lysine