Regulation of chromosome stability by the histone H2A variant Htz1, the Swr1 chromatin remodeling complex, and the histone acetyltransferase NuA4.
NuA4, the only essential histone acetyltransferase complex in Saccharomyces cerevisiae, acetylates the N-terminal tails of histones H4 and H2A. Affinity purification of NuA4 revealed the presence of three previously undescribed subunits, Vid21/Eaf1/Ydr359c, Swc4/Eaf2/Ygr002c, and Eaf7/Ynl136w. Experimental analyses revealed at least two functionally distinct sets of polypeptides in NuA4: (i) Vid21 and Yng2, and (ii) Eaf5 and Eaf7. Vid21 and Yng2 are required for bulk histone H4 acetylation and are functionally linked to the histone H2A variant Htz1 and the Swr1 ATPase complex (SWR-C) that assembles Htz1 into chromatin, whereas Eaf5 and Eaf7 have a different, as yet undefined, role. Mutations in Htz1, the SWR-C, and NuA4 cause defects in chromosome segregation that are consistent with genetic interactions we have observed between the genes encoding these proteins and genes encoding kinetochore components. Because SWR-C-dependent recruitment of Htz1 occurs in both transcribed and centromeric regions, a NuA4/SWR-C/Htz1 pathway may regulate both transcription and centromere function in S. cerevisiae.
Krogan
Nevan J
NJ
Banting and Best Department of Medical Research, University of Toronto, Toronto, Ontario, Canada M5G 1L6.
Baetz
Kristin
K
Keogh
Michael-Christopher
MC
Datta
Nira
N
Sawa
Chika
C
Kwok
Trevor C Y
TC
Thompson
Natalie J
NJ
Davey
Michael G
MG
Pootoolal
Jeff
J
Hughes
Timothy R
TR
Emili
Andrew
A
Buratowski
Stephen
S
Hieter
Philip
P
Greenblatt
Jack F
JF
D000123:Acetyltransferases / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism*; D042002:Chromatin Assembly and Disassembly; D043171:Chromosomal Instability / Q000235:genetics; D015825:Chromosomes, Fungal / Q000378:metabolism; D051548:Histone Acetyltransferases; D006657:Histones / Q000235:genetics* / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*
D006657:Histones; D029701:Saccharomyces cerevisiae Proteins; C477280:YAF9 protein, S cerevisiae; D000123:Acetyltransferases; D051548:Histone Acetyltransferases; D000251:Adenosine Triphosphatases; C481261:Swr1 protein, S cerevisiae