Gene Symbol: ESA1
Description: NuA4 histone acetyltransferase complex catalytic subunit ESA1
Alias: KAT5, TAS1, NuA4 histone acetyltransferase complex catalytic subunit ESA1
Species: Saccharomyces cerevisiae S288c

Top Publications

  1. Chang C, Clarke A, Pillus L. Suppression analysis of esa1 mutants in Saccharomyces cerevisiae links NAB3 to transcriptional silencing and nucleolar functions. G3 (Bethesda). 2012;2:1223-32 pubmed publisher
    The acetyltransferase Esa1 is essential in the yeast Saccharomyces cerevisiae and plays a critical role in multiple cellular processes. The most well-defined targets for Esa1 are lysine residues on histones...
  2. Decker P, Yu D, Iizuka M, Qiu Q, Smith M. Catalytic-site mutations in the MYST family histone Acetyltransferase Esa1. Genetics. 2008;178:1209-20 pubmed publisher
    b>Esa1 is the only essential histone acetyltransferase (HAT) in budding yeast...
  3. Formosa T, Ruone S, Adams M, Olsen A, Eriksson P, Yu Y, et al. Defects in SPT16 or POB3 (yFACT) in Saccharomyces cerevisiae cause dependence on the Hir/Hpc pathway: polymerase passage may degrade chromatin structure. Genetics. 2002;162:1557-71 pubmed
    ..Mutations that impair the reassembly activity cause chromatin to accumulate in an abnormally disrupted state, imposing a requirement for a nucleosome reassembly function that we propose is provided by Hir/Hpc proteins. ..
  4. Scott E, Pillus L. Homocitrate synthase connects amino acid metabolism to chromatin functions through Esa1 and DNA damage. Genes Dev. 2010;24:1903-13 pubmed publisher
    ..yeast is linked to the key process of DNA damage repair through the essential MYST family histone acetyltransferase Esa1 and the H2A.Z histone variant...
  5. Le Masson I, Yu D, Jensen K, Chevalier A, Courbeyrette R, Boulard Y, et al. Yaf9, a novel NuA4 histone acetyltransferase subunit, is required for the cellular response to spindle stress in yeast. Mol Cell Biol. 2003;23:6086-102 pubmed
    ..Although Esa1, the catalytic subunit of NuA4, is essential for viability, we found that yaf9 Delta mutants are viable but ..
  6. Allard S, Utley R, Savard J, Clarke A, Grant P, Brandl C, et al. NuA4, an essential transcription adaptor/histone H4 acetyltransferase complex containing Esa1p and the ATM-related cofactor Tra1p. EMBO J. 1999;18:5108-19 pubmed
    ..We have identified the catalytic subunit of the complex as the product of ESA1, an essential gene required for cell cycle progression in yeast...
  7. Keogh M, Mennella T, Sawa C, Berthelet S, Krogan N, Wolek A, et al. The Saccharomyces cerevisiae histone H2A variant Htz1 is acetylated by NuA4. Genes Dev. 2006;20:660-5 pubmed
    ..Function-specific modifications may help explain how the same component of chromatin can function in diverse pathways. ..
  8. Boudreault A, Cronier D, Selleck W, Lacoste N, Utley R, Allard S, et al. Yeast enhancer of polycomb defines global Esa1-dependent acetylation of chromatin. Genes Dev. 2003;17:1415-28 pubmed
    ..The picNuA4 complex contains Esa1, Epl1, and Yng2 as subunits and strongly prefers chromatin over free histones as substrate...
  9. Bird A, Yu D, Pray Grant M, Qiu Q, Harmon K, Megee P, et al. Acetylation of histone H4 by Esa1 is required for DNA double-strand break repair. Nature. 2002;419:411-5 pubmed
    ..Both pathways require the ESA1 histone acetyl transferase (HAT), which is responsible for acetylating all H4 tail lysines, including ectopic ..

More Information


  1. Ginsburg D, Govind C, Hinnebusch A. NuA4 lysine acetyltransferase Esa1 is targeted to coding regions and stimulates transcription elongation with Gcn5. Mol Cell Biol. 2009;29:6473-87 pubmed publisher
    ..The NuA4 KAT, Esa1, mediates increased H4 acetylation and enhanced RSC occupancy and histone eviction in coding sequences and ..
  2. Chang C, Pillus L. Collaboration between the essential Esa1 acetyltransferase and the Rpd3 deacetylase is mediated by H4K12 histone acetylation in Saccharomyces cerevisiae. Genetics. 2009;183:149-60 pubmed publisher
    ..In Saccharomyces cerevisiae, Esa1 and Rpd3 have opposing enzymatic activities and are catalytic subunits of multiple chromatin modifying complexes ..
  3. Auger A, Galarneau L, Altaf M, Nourani A, Doyon Y, Utley R, et al. Eaf1 is the platform for NuA4 molecular assembly that evolutionarily links chromatin acetylation to ATP-dependent exchange of histone H2A variants. Mol Cell Biol. 2008;28:2257-70 pubmed publisher
    Eaf1 (for Esa1-associated factor 1) and Eaf2 have been identified as stable subunits of NuA4, a yeast histone H4/H2A acetyltransferase complex implicated in gene regulation and DNA repair...
  4. Eisen A, Utley R, Nourani A, Allard S, Schmidt P, Lane W, et al. The yeast NuA4 and Drosophila MSL complexes contain homologous subunits important for transcription regulation. J Biol Chem. 2001;276:3484-91 pubmed
    ..The EAF3 deletion and the ESA1 mutation lead to a decrease in PHO5 gene expression; the EAF3 deletion also significantly reduces HIS4 and TRP4 ..
  5. Selleck W, Fortin I, Sermwittayawong D, Cote J, Tan S. The Saccharomyces cerevisiae Piccolo NuA4 histone acetyltransferase complex requires the Enhancer of Polycomb A domain and chromodomain to acetylate nucleosomes. Mol Cell Biol. 2005;25:5535-42 pubmed
    ..specific recognition of nucleosomes compared to naked histones, we have performed a functional dissection of the Esa1-containing Saccharomyces cerevisiae Piccolo NuA4 histone acetyltransferase complex...
  6. Knutson B, Hahn S. Domains of Tra1 important for activator recruitment and transcription coactivator functions of SAGA and NuA4 complexes. Mol Cell Biol. 2011;31:818-31 pubmed publisher
    ..Our results show that Tra1 recruitment at Gcn4-dependent and Rap1-dependent promoters requires the same regions of Tra1 and that separate regions of Tra1 contribute to the HAT activity and stability of the SAGA and NuA4 HAT modules. ..
  7. Berndsen C, Selleck W, McBryant S, Hansen J, Tan S, Denu J. Nucleosome recognition by the Piccolo NuA4 histone acetyltransferase complex. Biochemistry. 2007;46:2091-9 pubmed
  8. Clarke A, Samal E, Pillus L. Distinct roles for the essential MYST family HAT Esa1p in transcriptional silencing. Mol Biol Cell. 2006;17:1744-57 pubmed
    ..protein deacetylase Sir2p, and the acetylation levels of key Esa1p histone targets are reduced in the rDNA in esa1 mutants...
  9. Utley R, Lacoste N, Jobin Robitaille O, Allard S, Cote J. Regulation of NuA4 histone acetyltransferase activity in transcription and DNA repair by phosphorylation of histone H4. Mol Cell Biol. 2005;25:8179-90 pubmed
    ..These findings demonstrate that H4 phospho-serine 1 regulates chromatin acetylation by the NuA4 complex and that this process is important for normal gene expression and DNA repair. ..
  10. Galarneau L, Nourani A, Boudreault A, Zhang Y, Heliot L, Allard S, et al. Multiple links between the NuA4 histone acetyltransferase complex and epigenetic control of transcription. Mol Cell. 2000;5:927-37 pubmed
    ..Mutations in ACT3 and acetyltransferase-encoding ESA1 cause gene-specific transcription defects...
  11. Clarke A, Lowell J, Jacobson S, Pillus L. Esa1p is an essential histone acetyltransferase required for cell cycle progression. Mol Cell Biol. 1999;19:2515-26 pubmed
    ..Here we report characterization of ESA1, an essential gene that is a member of the MYST family that includes two yeast silencing genes, human genes ..
  12. Nourani A, Doyon Y, Utley R, Allard S, Lane W, Cote J. Role of an ING1 growth regulator in transcriptional activation and targeted histone acetylation by the NuA4 complex. Mol Cell Biol. 2001;21:7629-40 pubmed
    ..They also suggest that regulation of mammalian cell proliferation by p53-dependent transcriptional activation functions through recruitment of an ING1-containing histone acetyltransferase complex. ..
  13. Matangkasombut O, Buratowski S. Different sensitivities of bromodomain factors 1 and 2 to histone H4 acetylation. Mol Cell. 2003;11:353-63 pubmed
    ..A deletion of BDF1 but not BDF2 is lethal when combined with a mutant allele of ESA1 (a histone H4 acetyltransferase) or with nonacetylatable histone H4 variants...
  14. Loewith R, Meijer M, Lees Miller S, Riabowol K, Young D. Three yeast proteins related to the human candidate tumor suppressor p33(ING1) are associated with histone acetyltransferase activities. Mol Cell Biol. 2000;20:3807-16 pubmed
    ..Genetic and biochemical evidence indicate that the Yng2-associated HAT is Esa1, suggesting that Yng2 is a component of the NuA4 HAT complex...
  15. Zhang H, Richardson D, Roberts D, Utley R, Erdjument Bromage H, Tempst P, et al. The Yaf9 component of the SWR1 and NuA4 complexes is required for proper gene expression, histone H4 acetylation, and Htz1 replacement near telomeres. Mol Cell Biol. 2004;24:9424-36 pubmed
    ..Taken together, these data indicate that Yaf9 may function in NuA4 and SWR1 complexes to help antagonize silencing near telomeres. ..
  16. Herbig E, Warfield L, Fish L, Fishburn J, Knutson B, Moorefield B, et al. Mechanism of Mediator recruitment by tandem Gcn4 activation domains and three Gal11 activator-binding domains. Mol Cell Biol. 2010;30:2376-90 pubmed publisher
    ..Our combined results show gene-specific coactivator requirements, a surprising redundancy in activator-target interactions, and an activator-coactivator interaction mediated by multiple low-affinity protein-protein interactions. ..
  17. Kobor M, Venkatasubrahmanyam S, Meneghini M, Gin J, Jennings J, Link A, et al. A protein complex containing the conserved Swi2/Snf2-related ATPase Swr1p deposits histone variant H2A.Z into euchromatin. PLoS Biol. 2004;2:E131 pubmed
    ..Metazoan orthologs of Swr1p (Drosophila Domino; human SRCAP and p400) may have analogous functions...
  18. Ginsburg D, Anlembom T, Wang J, Patel S, Li B, Hinnebusch A. NuA4 links methylation of histone H3 lysines 4 and 36 to acetylation of histones H4 and H3. J Biol Chem. 2014;289:32656-70 pubmed publisher
  19. Huang J, Tan S. Piccolo NuA4-catalyzed acetylation of nucleosomal histones: critical roles of an Esa1 Tudor/chromo barrel loop and an Epl1 enhancer of polycomb A (EPcA) basic region. Mol Cell Biol. 2013;33:159-69 pubmed publisher
    ..While Piccolo NuA4's catalytic subunit Esa1 alone is unable to acetylate nucleosomal histones, its accessory subunits, Yng2 and Epl1, enable Esa1 to bind to ..
  20. Lottersberger F, Panza A, Lucchini G, Longhese M. Functional and physical interactions between yeast 14-3-3 proteins, acetyltransferases, and deacetylases in response to DNA replication perturbations. Mol Cell Biol. 2007;27:3266-81 pubmed
    ..Moreover, Bmh proteins physically interact, directly or indirectly, with the Esa1 acetyltransferase throughout the cell cycle and with the Rpd3 deacetylase specifically during unperturbed S phase ..
  21. Yi C, Ma M, Ran L, Zheng J, Tong J, Zhu J, et al. Function and molecular mechanism of acetylation in autophagy regulation. Science. 2012;336:474-7 pubmed publisher
    ..We used genetic analysis of Saccharomyces cerevisiae to identify Esa1 as a histone acetyltransferase required for autophagy...
  22. Uprety B, Sen R, Bhaumik S. Eaf1p Is Required for Recruitment of NuA4 in Targeting TFIID to the Promoters of the Ribosomal Protein Genes for Transcriptional Initiation In Vivo. Mol Cell Biol. 2015;35:2947-64 pubmed publisher
    ..Collectively, these results provide significant insights into the regulation of ribosomal protein gene expression and, hence, ribosome biogenesis and functions. ..
  23. Chittuluru J, Chaban Y, Monnet Saksouk J, Carrozza M, Sapountzi V, Selleck W, et al. Structure and nucleosome interaction of the yeast NuA4 and Piccolo-NuA4 histone acetyltransferase complexes. Nat Struct Mol Biol. 2011;18:1196-203 pubmed publisher
    ..Taken together, these results provide an understanding of the NuA4 subunit organization and the NuA4-NCP interactions. ..
  24. Zhou B, Wang S, Xu L, Meng F, Xuan Y, Duan Y, et al. SWR1 complex poises heterochromatin boundaries for antisilencing activity propagation. Mol Cell Biol. 2010;30:2391-400 pubmed publisher
    ..Our results support a model where SWR1-C resides at the heterochromatin boundary to maintain and amplify antisilencing activity of histone H4 acetylation through incorporating H2A.Z into chromatin. ..
  25. Stevens J, O Donnell A, Perry T, Benjamin J, Barnes C, Johnston G, et al. FACT, the Bur kinase pathway, and the histone co-repressor HirC have overlapping nucleosome-related roles in yeast transcription elongation. PLoS ONE. 2011;6:e25644 pubmed publisher
  26. Torres Machorro A, Pillus L. Bypassing the requirement for an essential MYST acetyltransferase. Genetics. 2014;197:851-63 pubmed publisher
    ..b>Esa1, like its human homolog Tip60, is an essential MYST family enzyme that acetylates histones H4 and H2A and other ..
  27. Downey M, Johnson J, Davey N, Newton B, Johnson T, Galaang S, et al. Acetylome profiling reveals overlap in the regulation of diverse processes by sirtuins, gcn5, and esa1. Mol Cell Proteomics. 2015;14:162-76 pubmed publisher
    ..To identify HATs that promote acetylation of these sites, we also performed this analysis in gcn5 (SAGA) and esa1 (NuA4) mutants. We observed strong sequence specificity for the sirtuins and for each of these HATs...
  28. Adachi N, Kimura A, Horikoshi M. A conserved motif common to the histone acetyltransferase Esa1 and the histone deacetylase Rpd3. J Biol Chem. 2002;277:35688-95 pubmed
    ..A particular pair of HAT (Esa1) and HDAC (Rpd3) is proposed to modify the same lysine residue in vitro and in vivo...
  29. Szerlong H, Hinata K, Viswanathan R, Erdjument Bromage H, Tempst P, Cairns B. The HSA domain binds nuclear actin-related proteins to regulate chromatin-remodeling ATPases. Nat Struct Mol Biol. 2008;15:469-76 pubmed publisher
    ..Taken together, we define the role of the HSA domain and provide evidence for a regulatory relationship involving the ARP-HSA module and two new functional domains conserved in remodeler ATPases that contain ARPs. ..
  30. Nourani A, Howe L, Pray Grant M, Workman J, Grant P, Cote J. Opposite role of yeast ING family members in p53-dependent transcriptional activation. J Biol Chem. 2003;278:19171-5 pubmed
    ..They also demonstrate the key specific role of ING proteins in different chromatin modifying complexes and their opposite functions in p53-dependent transcription. ..
  31. House N, Yang J, Walsh S, Moy J, Freudenreich C. NuA4 initiates dynamic histone H4 acetylation to promote high-fidelity sister chromatid recombination at postreplication gaps. Mol Cell. 2014;55:818-828 pubmed publisher
    ..Here we have utilized a repetitive DNA sequence that induces endogenous DNA damage to identify histone modifications that regulate recombination efficiency and fidelity during postreplication gap repair. ..
  32. Sathianathan A, Ravichandran P, Lippi J, Cohen L, Messina A, Shaju S, et al. The Eaf3/5/7 Subcomplex Stimulates NuA4 Interaction with Methylated Histone H3 Lys-36 and RNA Polymerase II. J Biol Chem. 2016;291:21195-21207 pubmed
    ..Overall, these results reveal the function of Eaf3/5/7 within NuA4 to be important for both NuA4 and RNA polymerase II binding. ..
  33. Steinboeck F, Bogusch A, Kaufmann A, Heidenreich E. The nuclear actin-related protein of Saccharomyces cerevisiae, Arp4, directly interacts with the histone acetyltransferase Esa1p. J Biochem. 2007;141:661-8 pubmed
    ..We propose that the interaction of Arp4 with Esa1p is crucial for proper functioning and targeting of the NuA4 complex. ..
  34. Verdone L, Wu J, Van Riper K, Kacherovsky N, Vogelauer M, Young E, et al. Hyperacetylation of chromatin at the ADH2 promoter allows Adr1 to bind in repressed conditions. EMBO J. 2002;21:1101-11 pubmed
  35. Chen J, Li Y, Pan X, Lei B, Chang C, Liu Z, et al. The fission yeast inhibitor of growth (ING) protein Png1p functions in response to DNA damage. J Biol Chem. 2010;285:15786-93 pubmed publisher
    ..both fission yeast PNG1 and MST1 can functionally complement their budding yeast correspondence homologs YNG2 and ESA1, respectively...
  36. Ruault M, Pillus L. Chromatin-modifiying enzymes are essential when the Saccharomyces cerevisiae morphogenesis checkpoint is constitutively activated. Genetics. 2006;174:1135-49 pubmed
    ..A catalytically dead Hsl7p retained wild-type interactions, implying that modification of histone H3 or H4 N termini by Gcn5p, Esa1p, Rpd3p, and Set1p, but not by Hsl7p, was needed to bypass the morphogenesis checkpoint. ..
  37. Morillon A, Karabetsou N, Nair A, Mellor J. Dynamic lysine methylation on histone H3 defines the regulatory phase of gene transcription. Mol Cell. 2005;18:723-34 pubmed
    ..This releases RNAPII from Isw1 control and promotes controlled transcription elongation and termination. We propose that newly initiated RNAPII is under epigenetic control. ..
  38. Torres Machorro A, Aris J, Pillus L. A moonlighting metabolic protein influences repair at DNA double-stranded breaks. Nucleic Acids Res. 2015;43:1646-58 pubmed publisher
    ..of a key role for Lys20 in DNA damage repair through its interaction with the MYST family histone acetyltransferase Esa1. Overexpression of Lys20 promotes suppression of DNA damage sensitivity of esa1 mutants...
  39. Searle N, Torres Machorro A, Pillus L. Chromatin Regulation by the NuA4 Acetyltransferase Complex Is Mediated by Essential Interactions Between Enhancer of Polycomb (Epl1) and Esa1. Genetics. 2017;205:1125-1137 pubmed publisher
    ..Among acetyltransferases, the NuA4 complex containing Tip60 or its Saccharomyces cerevisiae ortholog Esa1 is of particular significance because of its roles in crucial genomic processes including DNA damage repair and ..
  40. Gao Q, Madian A, Liu X, Adamec J, Regnier F. Coupling protein complex analysis to peptide based proteomics. J Chromatogr A. 2010;1217:7661-8 pubmed publisher
  41. Uprety B, Kaja A, Ferdoush J, Sen R, Bhaumik S. Regulation of Antisense Transcription by NuA4 Histone Acetyltransferase and Other Chromatin Regulatory Factors. Mol Cell Biol. 2016;36:992-1006 pubmed publisher
    ..Taken together, our results demonstrate for the first time the roles of NuA4 KAT and other chromatin regulatory factors in controlling antisense transcription, thus illuminating chromatin regulation of antisense transcription. ..
  42. Bonetti D, Anbalagan S, Lucchini G, Clerici M, Longhese M. Tbf1 and Vid22 promote resection and non-homologous end joining of DNA double-strand break ends. EMBO J. 2013;32:275-89 pubmed publisher
    ..Finally, inactivation of either Tbf1 or Vid22 impairs nucleosome eviction around the DSB, suggesting that these proteins promote efficient repair of the break by influencing chromatin identity in its surroundings. ..
  43. Torres Machorro A, Clark L, Chang C, Pillus L. The Set3 Complex Antagonizes the MYST Acetyltransferase Esa1 in the DNA Damage Response. Mol Cell Biol. 2015;35:3714-25 pubmed publisher
    ..The essential MYST family Esa1 KAT acetylates core histones and many nonhistone substrates...
  44. Suka N, Luo K, Grunstein M. Sir2p and Sas2p opposingly regulate acetylation of yeast histone H4 lysine16 and spreading of heterochromatin. Nat Genet. 2002;32:378-83 pubmed
    ..These data indicate that opposing effects of Sir2p and Sas2p on acetylation of H4-Lys16 maintain the boundary at telomeric heterochromatin. ..
  45. Joo Y, Kim J, Kang U, Yu M, Kim J. Gcn4p-mediated transcriptional repression of ribosomal protein genes under amino-acid starvation. EMBO J. 2011;30:859-72 pubmed publisher
    ..Moreover, our results showed evidence of a novel link between general control of amino-acid biosynthesis and ribosome biogenesis mediated by Gcn4p at an early stage of adaptation to amino-acid starvation. ..
  46. Kimura A, Adachi N, Horikoshi M. Series of vectors to evaluate the position and the order of two different affinity tags for purification of protein complexes. Anal Biochem. 2003;314:253-9 pubmed
    ..These vectors provide a convenient way to select the best position of tags for efficient purification of protein complexes also applicable in proteomics studies. ..
  47. Renaud Young M, Lloyd D, Chatfield Reed K, George I, Chua G, Cobb J. The NuA4 complex promotes translesion synthesis (TLS)-mediated DNA damage tolerance. Genetics. 2015;199:1065-76 pubmed publisher
    ..Genetic analyses in Saccharomyces cerevisiae showed synergistic sensitivity to MMS when NuA4 alleles, esa1-L254P and yng2Δ, were combined with the error-free bypass mutant ubc13Δ...
  48. Lindstrom K, Vary J, Parthun M, Delrow J, Tsukiyama T. Isw1 functions in parallel with the NuA4 and Swr1 complexes in stress-induced gene repression. Mol Cell Biol. 2006;26:6117-29 pubmed
    ..In contrast to a recruitment-based model, we find that the NuA4 and Swr1 complexes act throughout the genome while only a specific subset of the genome shows alterations in transcription. ..
  49. Kuo Y, Henry R, Tan S, Côté J, Andrews A. Site specificity analysis of Piccolo NuA4-mediated acetylation for different histone complexes. Biochem J. 2015;472:239-48 pubmed publisher
    ..Such findings provide valuable insight into regulating Piccolo NuA4 specificity by modulating chromatin dynamics and in turn manipulating gene expression. ..
  50. Berndsen C, Albaugh B, Tan S, Denu J. Catalytic mechanism of a MYST family histone acetyltransferase. Biochemistry. 2007;46:623-9 pubmed
    ..Here, using the prototypical MYST family member Esa1, and its physiological complex (piccolo NuA4), steady-state kinetic analyses revealed a kinetic mechanism that ..
  51. Rollins M, Huard S, Morettin A, Takuski J, Pham T, Fullerton M, et al. Lysine acetyltransferase NuA4 and acetyl-CoA regulate glucose-deprived stress granule formation in Saccharomyces cerevisiae. PLoS Genet. 2017;13:e1006626 pubmed publisher
    ..Altogether this work establishes both NuA4 and the metabolite acetyl-CoA as critical signaling pathways regulating the formation of glucose-deprived stress granules. ..
  52. Xu P, Li C, Chen Z, Jiang S, Fan S, Wang J, et al. The NuA4 Core Complex Acetylates Nucleosomal Histone H4 through a Double Recognition Mechanism. Mol Cell. 2016;63:965-75 pubmed publisher
    ..The combined data reveal a space-sequence double recognition mechanism of the histone tails by a modifying enzyme in the context of the nucleosome. ..
  53. Lu J, Lin Y, Sheu J, Wu J, Lee F, Chen Y, et al. Acetylation of yeast AMPK controls intrinsic aging independently of caloric restriction. Cell. 2011;146:969-79 pubmed publisher
    ..We propose a protein acetylation-phosphorylation cascade that regulates Sch9 activity, controls intrinsic aging, and extends replicative life span in yeast. ..
  54. Shimojo H, Sano N, Moriwaki Y, Okuda M, Horikoshi M, Nishimura Y. Novel structural and functional mode of a knot essential for RNA binding activity of the Esa1 presumed chromodomain. J Mol Biol. 2008;378:987-1001 pubmed publisher
    ..Here we propose a novel binding mode for chromodomain-RNA interactions. Essential Sas-related acetyltransferase 1 (Esa1) contains a presumed chromodomain in addition to a histone acetyltransferase domain...