Abstract
Longstanding observations suggest that acetylation and/or amino-terminal tail structure of histones H3 and H4 are critical for eukaryotic cells. For Saccharomyces cerevisiae, loss of a single H4-specific histone acetyltransferase (HAT), Esa1p, results in cell cycle defects and death. In contrast, although several yeast HAT complexes preferentially acetylate histone H3, the catalytic subunits of these complexes are not essential for viability. To resolve the apparent paradox between the significance of H3 versus H4 acetylation, we tested the hypothesis that H3 modification is essential, but is accomplished through combined activities of two enzymes. We observed that Sas3p and Gcn5p HAT complexes have overlapping patterns of acetylation. Simultaneous disruption of SAS3, the homolog of the MOZ leukemia gene, and GCN5, the hGCN5/PCAFhomolog, is synthetically lethal due to loss of acetyltransferase activity. This key combination of activities is specific for these two HATs because neither is synthetically lethal with mutations of other MYST family or H3-specific acetyltransferases. Further, the combined loss of GCN5 and SAS3 functions results in an extensive, global loss of H3 acetylation and arrest in the G2/M phase of the cell cycle. The strikingly similar effect of loss of combined essential H3 HAT activities and the loss of a single essential H4 HAT underscores the fundamental biological significance of each of these chromatin-modifying activities.
References
70
Referenced
187
- Adams A. Gottschling D.E. Kaiser C.A. Stearns T. (1997) Methods in yeast genetics: A Cold Spring Harbor Laboratory course manual. (Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY).
10.1093/emboj/18.18.5108
10.1006/jmbi.1999.3338
- Ausubel F.M. (1987) Current protocols in molecular biology. (Greene Pub. Associates and Wiley-Interscience, J. Wiley, NY).
10.1128/MCB.20.2.634-647.2000
10.1128/MCB.19.4.2515
/ Mol. Cell. Biol. / Esa1p is an essential histone acetyltransferase required for cell cycle progression. by Clarke (1999)10.1006/meth.1998.0635
10.1128/MCB.19.10.6621
/ Mol. Cell. Biol. / The ADA complex is a distinct histone acetyltransferase complex in Saccharomyces cerevisiae. by Eberharter (1999)10.1101/gad.10.10.1247
10.1093/genetics/145.4.923
/ Genetics / The role of Sas2, an acetyltransferase homologue of Saccharomyces cerevisiae, in silencing and ORC function. by Ehrenhofer-Murray (1997)10.1093/nar/27.9.2022
10.1016/S0021-9258(18)41815-7
/ J. Biol. Chem. / Role of the histone “tails” in the folding of oligonuclesomes depleted of histone H1. by García-Ramirez (1992)10.1002/j.1460-2075.1992.tb05507.x
/ EMBO J. / Two distinct yeast transcriptional activators require the function of the GCN5 protein to promote normal levels of transcription. by Georgakopoulos (1992)10.1007/BF00290718
10.1101/gad.11.13.1640
10.1074/jbc.274.9.5895
10.1016/S0092-8674(01)00279-3
10.1615/CritRevEukarGeneExpr.v9.i3-4.80
10.1074/jbc.274.33.23027
10.1016/S0959-437X(99)80027-6
10.1101/gad.14.10.1196
/ Genes & Dev. / The something about silencing protein, Sas3, is the catalytic subunit of NuA3, a yTAF(II)30-containing HAT complex that interacts with the Spt16 subunit of the yeast CP (Cdc68/Pob3)-FACT complex. by John (2000)10.1101/gad.13.11.1412
10.1016/S0092-8674(00)00081-7
10.1038/383269a0
10.1101/gad.12.5.627
10.1016/S1097-2765(00)00129-5
10.1016/S0006-3495(88)83126-6
10.1101/gad.10.6.686
10.1016/S1097-2765(00)00021-6
10.1002/j.1460-2075.1994.tb06806.x
/ EMBO J. / Functional similarity an physical association between GCN5 and ADA2: Putative transcriptional adaptors. by Marcus (1994)10.1128/MCB.16.6.3197
/ Mol. Cell. Biol. / ADA5/SPT20 links the ADA and SPT genes, which are involved in yeast transcription. by Marcus (1996)10.1126/science.2106160
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/ Mol. Cell. Biol. / The highly conserved N-terminal domains of histones H3 and H4 are required for normal cell cycle progression. by Morgan (1991)10.1128/MCB.18.11.6293
/ Mol. Cell. Biol. / Persistent interactions of core histone tails with nucleosomal DNA following acetylation and transcription factor binding. by Mutskov (1998)10.1016/0092-8674(89)90920-3
10.1016/S0960-9822(99)80160-2
10.1016/S0092-8674(00)80903-4
10.1038/22350
10.1016/S1097-2765(00)80181-1
10.1038/35020675
10.1128/MCB.18.2.1049
/ Mol. Cell. Biol. / Mutations in chromatin components suppress a defect of Gcn5 protein in Saccharomyces cerevisiae. by Perez-Martin (1998)10.1073/pnas.91.8.2905
10.1128/MCB.17.11.6212
/ Mol. Cell. Biol. / Role of ADA/GCN5 products in antagonizing chromatin-mediated transcriptional repression. by Pollard (1997)10.1038/ng0996-42
10.1128/MCB.16.6.3206
/ Mol. Cell. Biol. / SPT20/ADA5 encodes a novel protein functionally related to the TATA-binding protein and important for transcription in Saccharomyces cerevisiae. by Roberts (1996)10.1093/genetics/147.2.451
/ Genetics / Essential functional interactions of SAGA, a Saccharomyces cerevisiae complex of Spt, Ada, and Gcn5 proteins, with the Snf/Swi and Srb/mediator complexes. (1997)10.1146/annurev.biochem.70.1.81
10.1016/S0014-5793(97)00049-5
10.1074/jbc.272.9.5571
10.1093/genetics/155.4.1593
/ Genetics / POB3 is required for both transcription and replication in the yeast Saccharomyces cerevisiae. by Schlesinger (2000)10.1074/jbc.M003783200
10.1073/pnas.95.7.3561
10.1128/MMBR.64.2.435-459.2000
10.1128/MCB.19.1.86
/ Mol. Cell. Biol. / Functional organization of the yeast SAGA complex: Distinct components involved in structural integrity, nucleosome acetylation, and TATA-binding protein interaction. by Sterner (1999)10.1038/47412
10.1074/jbc.273.38.24414
10.1128/MCB.18.8.4707
/ Mol. Cell. Biol. / Nuclear proteins Nut1p and Nut2p cooperate to negatively regulate a Swi4p-dependent lacZ reporter gene in Saccharomyces cerevisiae. by Tabtiang (1998)10.1006/bbrc.1999.1836
10.1074/jbc.273.49.32388
10.1038/28886
10.1093/emboj/19.11.2629
10.1038/35044127
10.1101/gad.12.5.640
10.1074/jbc.M004998200
10.1074/jbc.275.17.13007
10.1128/MCB.17.7.4178
/ Mol. Cell. Biol. / The Saccharomyces cerevisiae DNA polymerase alpha catalytic subunit interacts with Cdc68/Spt16 and with Pob3, a protein similar to an HMG1-like protein. by Wittmeyer (1997)10.1093/emboj/19.12.3060
10.1016/S1097-2765(00)00116-7
10.1128/MCB.20.7.2350-2357.2000
10.1093/emboj/17.11.3155
Dates
Type | When |
---|---|
Created | 23 years, 1 month ago (July 26, 2002, 7:59 p.m.) |
Deposited | 3 years, 9 months ago (Nov. 15, 2021, 10:54 a.m.) |
Indexed | 3 weeks, 5 days ago (Aug. 6, 2025, 8:53 a.m.) |
Issued | 23 years, 9 months ago (Dec. 1, 2001) |
Published | 23 years, 9 months ago (Dec. 1, 2001) |
Published Online | 23 years, 9 months ago (Dec. 1, 2001) |
Published Print | 23 years, 9 months ago (Dec. 1, 2001) |
@article{Howe_2001, title={Histone H3 specific acetyltransferases are essential for cell cycle progression}, volume={15}, ISSN={1549-5477}, url={http://dx.doi.org/10.1101/gad.931401}, DOI={10.1101/gad.931401}, number={23}, journal={Genes & Development}, publisher={Cold Spring Harbor Laboratory}, author={Howe, LeAnn and Auston, Darryl and Grant, Patrick and John, Sam and Cook, Richard G. and Workman, Jerry L. and Pillus, Lorraine}, year={2001}, month=dec, pages={3144–3154} }