Gene Symbol: HHF1
Description: histone H4
Alias: histone H4
Species: Saccharomyces cerevisiae S288c
Products:     HHF1

Top Publications

  1. Feser J, Truong D, Das C, Carson J, KIEFT J, Harkness T, et al. Elevated histone expression promotes life span extension. Mol Cell. 2010;39:724-35 pubmed publisher
    ..This study indicates that maintenance of the fundamental chromatin structure is critical for slowing down the aging process and reveals that increasing the histone supply extends life span. ..
  2. Hecht A, Laroche T, Strahl Bolsinger S, Gasser S, Grunstein M. Histone H3 and H4 N-termini interact with SIR3 and SIR4 proteins: a molecular model for the formation of heterochromatin in yeast. Cell. 1995;80:583-92 pubmed
    ..Based on these interactions, we propose a model for heterochromatin-mediated transcriptional silencing in yeast, which may serve as a paradigm for other eukaryotic organisms as well. ..
  3. Schiza V, Molina Serrano D, Kyriakou D, Hadjiantoniou A, Kirmizis A. N-alpha-terminal acetylation of histone H4 regulates arginine methylation and ribosomal DNA silencing. PLoS Genet. 2013;9:e1003805 pubmed publisher
    ..acetyltransferase (Nat4) activity results specifically in increased deposition of asymmetric dimethylation of histone H4 arginine 3 (H4R3me2a) and in enhanced ribosomal-DNA silencing...
  4. Morillo Huesca M, Maya D, Muñoz Centeno M, Singh R, Oreal V, Reddy G, et al. FACT prevents the accumulation of free histones evicted from transcribed chromatin and a subsequent cell cycle delay in G1. PLoS Genet. 2010;6:e1000964 pubmed publisher
  5. Lacoste N, Utley R, Hunter J, Poirier G, Cote J. Disruptor of telomeric silencing-1 is a chromatin-specific histone H3 methyltransferase. J Biol Chem. 2002;277:30421-4 pubmed
    ..While Rmt1 methylates histone H4, Dot1 targets histone H3...
  6. Meluh P, Yang P, Glowczewski L, Koshland D, Smith M. Cse4p is a component of the core centromere of Saccharomyces cerevisiae. Cell. 1998;94:607-13 pubmed
    ..cerevisiae. In histone H4 and Cse4p mutants, the core centromere chromatin structure is disrupted at restrictive temperature...
  7. Johnson L, Kayne P, Kahn E, Grunstein M. Genetic evidence for an interaction between SIR3 and histone H4 in the repression of the silent mating loci in Saccharomyces cerevisiae. Proc Natl Acad Sci U S A. 1990;87:6286-90 pubmed
    ..This silencing is known to require at least five proteins (SIR1, SIR2, SIR3, SIR4, and histone H4) and is accompanied by a change in chromatin structure...
  8. Scorgie J, Donham D, Churchill M. Analysis of histone chaperone antisilencing function 1 interactions. Methods Enzymol. 2012;512:223-41 pubmed publisher
  9. Carmen A, Milne L, Grunstein M. Acetylation of the yeast histone H4 N terminus regulates its binding to heterochromatin protein SIR3. J Biol Chem. 2002;277:4778-81 pubmed
    ..This involves the interaction between the C terminus of SIR3 and the N terminus of histone H4. Since H4 is hypoacetylated in heterochromatin we wished to determine whether acetylation is involved in ..

More Information


  1. Hong J, Feng H, Zhou Z, Ghirlando R, Bai Y. Identification of functionally conserved regions in the structure of the chaperone/CenH3/H4 complex. J Mol Biol. 2013;425:536-45 pubmed publisher
    ..Thus, our studies have identified conserved structural bases of how the chaperones recognize CenH3 and perform the chaperone function. ..
  2. Green E, Mas G, Young N, Garcia B, Gozani O. Methylation of H4 lysines 5, 8 and 12 by yeast Set5 calibrates chromatin stress responses. Nat Struct Mol Biol. 2012;19:361-3 pubmed publisher
    ..Here we identify Set5 as the first histone H4 methyltransferase, which monomethylates the critical H4 lysine residues 5, 8 and 12 in budding yeast...
  3. Singh R, Kabbaj M, Paik J, Gunjan A. Histone levels are regulated by phosphorylation and ubiquitylation-dependent proteolysis. Nat Cell Biol. 2009;11:925-33 pubmed publisher
    ..Regulated histone proteolysis has major implications for the maintenance of epigenetic marks on chromatin, genomic stability and the packaging of sperm DNA. ..
  4. Wu W, Alami S, Luk E, Wu C, Sen S, Mizuguchi G, et al. Swc2 is a widely conserved H2AZ-binding module essential for ATP-dependent histone exchange. Nat Struct Mol Biol. 2005;12:1064-71 pubmed
    ..Finally, the C-terminal alpha-helix of H2AZ is crucial for its recognition by SWR1. These findings provide insight on the initial events of histone exchange. ..
  5. Poveda A, Sendra R. Site specificity of yeast histone acetyltransferase B complex in vivo. FEBS J. 2008;275:2122-36 pubmed publisher
    ..Previous studies performed with synthetic N-terminal histone H4 peptides found that whereas the HAT-B complex acetylates only Lys12, recombinant Hat1 is able to modify Lys12 ..
  6. Eriksson P, Mendiratta G, McLaughlin N, Wolfsberg T, Mariño Ramírez L, Pompa T, et al. Global regulation by the yeast Spt10 protein is mediated through chromatin structure and the histone upstream activating sequence elements. Mol Cell Biol. 2005;25:9127-37 pubmed
    ..No other high-affinity sites are predicted in the yeast genome. Thus, Spt10p is a sequence-specific activator of the histone genes, possessing a DNA-binding domain fused to a likely HAT domain. ..
  7. 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. ..
  8. Mellone B, Ball L, Suka N, Grunstein M, Partridge J, Allshire R. Centromere silencing and function in fission yeast is governed by the amino terminus of histone H3. Curr Biol. 2003;13:1748-57 pubmed
    ..Surprisingly, silent centromeric chromatin does not require the conserved lysine 8 and 16 residues of histone H4. To date, mutation of conserved N-terminal residues in endogenous histone genes has only been performed in ..
  9. Liu W, Roemer S, Port A, Churchill M. CAF-1-induced oligomerization of histones H3/H4 and mutually exclusive interactions with Asf1 guide H3/H4 transitions among histone chaperones and DNA. Nucleic Acids Res. 2012;40:11229-39 pubmed publisher
    ..Thus, transition of H3/H4 from the Asf1-associated dimer to the DNA-associated tetramer is promoted by CAF-1-induced H3/H4 oligomerization. ..
  10. VanDemark A, Blanksma M, Ferris E, Heroux A, Hill C, Formosa T. The structure of the yFACT Pob3-M domain, its interaction with the DNA replication factor RPA, and a potential role in nucleosome deposition. Mol Cell. 2006;22:363-74 pubmed
    ..These results support the model that the FACT family has an essential role in constructing nucleosomes during DNA replication, and suggest that RPA contributes to this process. ..
  11. Agez M, Chen J, Guerois R, van Heijenoort C, Thuret J, Mann C, et al. Structure of the histone chaperone ASF1 bound to the histone H3 C-terminal helix and functional insights. Structure. 2007;15:191-9 pubmed
    ..Point mutations that perturb the Asf1/histone interface were designed from the structure. The decreased binding affinity of the Asf1-H3/H4 complex correlates with decreased levels of H3-K56 acetylation and phenotypic defects in vivo. ..
  12. Glowczewski L, Yang P, Kalashnikova T, Santisteban M, Smith M. Histone-histone interactions and centromere function. Mol Cell Biol. 2000;20:5700-11 pubmed
    ..The histone H4 allele hhf1-20 confers defects in core centromere chromatin structure and mitotic chromosome transmission...
  13. Grant P, Eberharter A, John S, Cook R, Turner B, Workman J. Expanded lysine acetylation specificity of Gcn5 in native complexes. J Biol Chem. 1999;274:5895-900 pubmed
    ..Furthermore Ada and SAGA have overlapping, yet distinct, patterns of acetylation, suggesting that the association of specific subunits determines site specificity. ..
  14. Imai S, Armstrong C, Kaeberlein M, Guarente L. Transcriptional silencing and longevity protein Sir2 is an NAD-dependent histone deacetylase. Nature. 2000;403:795-800 pubmed
    ..Mutational studies indicate that lysine 16 in the amino-terminal tail of histone H4 and lysines 9, 14 and 18 in H3 are critically important in silencing, whereas lysines 5, 8 and 12 of H4 have ..
  15. Fry C, Norris A, Cosgrove M, Boeke J, Peterson C. The LRS and SIN domains: two structurally equivalent but functionally distinct nucleosomal surfaces required for transcriptional silencing. Mol Cell Biol. 2006;26:9045-59 pubmed
    ..Our study shows that structurally similar nucleosomal surfaces provide distinct functionalities in vivo and in vitro. ..
  16. 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
    The Sir3 protein helps form telomeric heterochromatin by interacting with hypoacetylated histone H4 lysine 16 (H4-Lys16). The molecular nature of the heterochromatin boundary is still unknown...
  17. Clemente Ruiz M, Prado F. Chromatin assembly controls replication fork stability. EMBO Rep. 2009;10:790-6 pubmed publisher
    ..forks is tightly connected with chromatin assembly, a process that can be impaired by the partial depletion of histone H4 leading to recombinogenic DNA damage...
  18. Georgel P, Palacios DeBeer M, Pietz G, Fox C, Hansen J. Sir3-dependent assembly of supramolecular chromatin structures in vitro. Proc Natl Acad Sci U S A. 2001;98:8584-9 pubmed
    ..Based on these data we hypothesize that Sir3p functions, at least in part, by mediating reorganization of the canonical chromatin fiber into functionally specialized higher order chromosomal domains. ..
  19. Su D, Hu Q, Li Q, Thompson J, Cui G, Fazly A, et al. Structural basis for recognition of H3K56-acetylated histone H3-H4 by the chaperone Rtt106. Nature. 2012;483:104-7 pubmed publisher
    ..We show that the Rtt106-(H3-H4)(2) interaction is important for gene silencing and the DNA damage response. ..
  20. Mizuguchi G, Xiao H, Wisniewski J, Smith M, Wu C. Nonhistone Scm3 and histones CenH3-H4 assemble the core of centromere-specific nucleosomes. Cell. 2007;129:1153-64 pubmed
    ..Bacterially expressed Scm3 binds directly to and reconstitutes a stoichiometric complex with Cse4 and histone H4 but not with conventional histone H3 and H4...
  21. Johnson A, Li G, Sikorski T, Buratowski S, Woodcock C, Moazed D. Reconstitution of heterochromatin-dependent transcriptional gene silencing. Mol Cell. 2009;35:769-81 pubmed publisher
    ..Sir3 binds to nucleosomes containing deacetylated histone H4 lysine 16 (H4K16) and, with Sir4, promotes spreading of Sir2 and deacetylation along the chromatin fiber...
  22. Shia W, Li B, Workman J. SAS-mediated acetylation of histone H4 Lys 16 is required for H2A.Z incorporation at subtelomeric regions in Saccharomyces cerevisiae. Genes Dev. 2006;20:2507-12 pubmed
    ..Z incorporation near telomeres. The presence of H4 Lys 16 acetylation and H2A.Z synergistically prevent the ectopic propagation of heterochromatin. Overall, our data suggest a novel antisilencing mechanism near telomeres. ..
  23. Camahort R, Shivaraju M, Mattingly M, Li B, Nakanishi S, Zhu D, et al. Cse4 is part of an octameric nucleosome in budding yeast. Mol Cell. 2009;35:794-805 pubmed publisher
    ..Taken together, our experimental evidence supports the model that the Cse4 nucleosome is an octamer, containing two copies each of Cse4, H2A, H2B, and H4. ..
  24. Prado F, Aguilera A. Partial depletion of histone H4 increases homologous recombination-mediated genetic instability. Mol Cell Biol. 2005;25:1526-36 pubmed
    ..connection between DNA replication and nucleosome assembly, we analyzed the effect of a partial depletion of histone H4 on genetic instability mediated by homologous recombination...
  25. Gunjan A, Verreault A. A Rad53 kinase-dependent surveillance mechanism that regulates histone protein levels in S. cerevisiae. Cell. 2003;115:537-49 pubmed
    ..Our results argue that Rad53 contributes to genome stability independently of Mec1 by preventing the damaging effects of excess histones both during normal cell cycle progression and in response to DNA damage. ..
  26. Ye J, Ai X, Eugeni E, Zhang L, Carpenter L, Jelinek M, et al. Histone H4 lysine 91 acetylation a core domain modification associated with chromatin assembly. Mol Cell. 2005;18:123-30 pubmed
    The acetylation of the NH2-terminal tail of histone H4 by type B histone acetyltransferases (HATs) is involved in the process of chromatin assembly...
  27. Adkins M, Carson J, English C, Ramey C, Tyler J. The histone chaperone anti-silencing function 1 stimulates the acetylation of newly synthesized histone H3 in S-phase. J Biol Chem. 2007;282:1334-40 pubmed
    ..These results demonstrate that Asf1 does not affect the stability of the newly synthesized histones per se, but instead histone binding by Asf1 promotes the efficient acetylation of specific residues of newly synthesized histone H3. ..
  28. Santisteban M, Kalashnikova T, Smith M. Histone H2A.Z regulats transcription and is partially redundant with nucleosome remodeling complexes. Cell. 2000;103:411-22 pubmed
    ..These results describe a novel pathway for regulating transcription using variant histones to modulate chromatin structure. ..
  29. White C, Suto R, Luger K. Structure of the yeast nucleosome core particle reveals fundamental changes in internucleosome interactions. EMBO J. 2001;20:5207-18 pubmed
    ..Finally, the yeast nucleosome core particle provides a structural context by which to interpret genetic data obtained from yeast. Coordinates have been deposited with the Protein Data Bank under accession number 1ID3. ..
  30. Kuo M, Xu X, Bolck H, Guo D. Functional connection between histone acetyltransferase Gcn5p and methyltransferase Hmt1p. Biochim Biophys Acta. 2009;1789:395-402 pubmed publisher
    ..Here we show that the budding yeast histone H4 arginine 3 (R3) methyltransferase Hmt1p binds acetylated histones H3 and H4, and importantly, that acetylated H4 ..
  31. Campos E, Fillingham J, Li G, Zheng H, Voigt P, Kuo W, et al. The program for processing newly synthesized histones H3.1 and H4. Nat Struct Mol Biol. 2010;17:1343-51 pubmed publisher
    ..We further demonstrate the high degree of conservation for this pathway between higher and lower eukaryotes. ..
  32. Natsume R, Eitoku M, Akai Y, Sano N, Horikoshi M, Senda T. Structure and function of the histone chaperone CIA/ASF1 complexed with histones H3 and H4. Nature. 2007;446:338-41 pubmed
    ..The carboxy-terminal beta-strand of histone H4 changes its partner from the beta-strand in histone H2A to that of CIA-I through large conformational change...
  33. Mizuguchi G, Shen X, Landry J, Wu W, Sen S, Wu C. ATP-driven exchange of histone H2AZ variant catalyzed by SWR1 chromatin remodeling complex. Science. 2004;303:343-8 pubmed
    ..These findings define a previously unknown role for the adenosine triphosphate-dependent chromatin remodeling machinery. ..
  34. Altaf M, Utley R, Lacoste N, Tan S, Briggs S, Cote J. Interplay of chromatin modifiers on a short basic patch of histone H4 tail defines the boundary of telomeric heterochromatin. Mol Cell. 2007;28:1002-14 pubmed
    ..We found that histone H4 N-terminal domain, unlike other histone tails, interacts with Dot1 and is essential for H3 K79 methylation...
  35. Zhou Z, Feng H, Zhou B, Ghirlando R, Hu K, Zwolak A, et al. Structural basis for recognition of centromere histone variant CenH3 by the chaperone Scm3. Nature. 2011;472:234-7 pubmed publisher
    ..Scm3(CBD) induces major conformational changes and sterically occludes DNA-binding sites in the structure of Cse4 and H4. These findings have implications for the assembly and architecture of the centromeric nucleosome. ..
  36. Yu Y, Srinivasan M, Nakanishi S, Leatherwood J, Shilatifard A, Sternglanz R. A conserved patch near the C terminus of histone H4 is required for genome stability in budding yeast. Mol Cell Biol. 2011;31:2311-25 pubmed publisher
  37. English C, Maluf N, Tripet B, Churchill M, Tyler J. ASF1 binds to a heterodimer of histones H3 and H4: a two-step mechanism for the assembly of the H3-H4 heterotetramer on DNA. Biochemistry. 2005;44:13673-82 pubmed
    ..We demonstrate that Asf1 blocks formation of the H3-H4 heterotetramer by a mechanism that likely involves occlusion of the H3-H3 dimerization interface. ..
  38. Park Y, Sudhoff K, Andrews A, Stargell L, Luger K. Histone chaperone specificity in Rtt109 activation. Nat Struct Mol Biol. 2008;15:957-64 pubmed
    ..Nap1 and Vps75 interact with histones and Rtt109 with comparable affinities. However, only Vps75 stimulates Rtt109 enzymatic activity. Our data highlight the functional specificity of Vps75 in Rtt109 activation. ..
  39. Oppikofer M, Kueng S, Martino F, Soeroes S, Hancock S, Chin J, et al. A dual role of H4K16 acetylation in the establishment of yeast silent chromatin. EMBO J. 2011;30:2610-21 pubmed publisher
    ..We conclude that acetylated H4K16 has a dual role in silencing: it recruits Sir2-4 and repels Sir3. Moreover, the deacetylation of H4K16(ac) by Sir2 actively promotes the high-affinity binding of the SIR holocomplex. ..
  40. Smith M, Yang P, Santisteban M, Boone P, Goldstein A, Megee P. A novel histone H4 mutant defective in nuclear division and mitotic chromosome transmission. Mol Cell Biol. 1996;16:1017-26 pubmed
    ..Here we report the first isolation of a temperature-sensitive lethal histone H4 mutant defective in mitotic chromosome transmission Saccharomyces cerevisiae...
  41. Onishi M, Liou G, Buchberger J, Walz T, Moazed D. Role of the conserved Sir3-BAH domain in nucleosome binding and silent chromatin assembly. Mol Cell. 2007;28:1015-28 pubmed
    ..histone-tail-binding domain and that its binding to nucleosomes is regulated by residues in the N terminus of histone H4 and the globular domain of histone H3 on the exposed surface of the nucleosome...
  42. Shen X, Ranallo R, Choi E, Wu C. Involvement of actin-related proteins in ATP-dependent chromatin remodeling. Mol Cell. 2003;12:147-55 pubmed
    ..GST-Arp8 binds preferentially to histones H3 and H4 in vitro, suggesting a histone chaperone function. These findings show direct involvement of Arps in the chromatin-remodeling process. ..
  43. Green E, Antczak A, Bailey A, Franco A, Wu K, Yates J, et al. Replication-independent histone deposition by the HIR complex and Asf1. Curr Biol. 2005;15:2044-9 pubmed
    ..These data indicate that the HIR complex and Asf1 proteins function together as a conserved eukaryotic pathway for histone replacement throughout the cell cycle. ..
  44. Song O, Wang X, Waterborg J, Sternglanz R. An Nalpha-acetyltransferase responsible for acetylation of the N-terminal residues of histones H4 and H2A. J Biol Chem. 2003;278:38109-12 pubmed
    ..Thus, Nat4 may be dedicated specifically to the N-terminal acetylation of histones H4 and H2A. Surprisingly, nat4 mutants grow at a normal rate and have no readily observable phenotypes. ..
  45. Santisteban M, Arents G, Moudrianakis E, Smith M. Histone octamer function in vivo: mutations in the dimer-tetramer interfaces disrupt both gene activation and repression. EMBO J. 1997;16:2493-506 pubmed
    Within the core histone octamer each histone H4 interacts with each H2A-H2B dimer subunit through two binding surfaces...
  46. Xiao H, Mizuguchi G, Wisniewski J, Huang Y, Wei D, Wu C. Nonhistone Scm3 binds to AT-rich DNA to organize atypical centromeric nucleosome of budding yeast. Mol Cell. 2011;43:369-80 pubmed publisher
    ..These findings suggest a model in which centromere-bound Scm3 aids recruitment of Cse4/H4 to assemble and maintain an H2A/H2B-deficient centromeric nucleosome. ..
  47. 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
    ..mutant alleles abolish enzymatic activity in vitro and result in partial loss of an acetylated isoform of histone H4 in vivo...
  48. Martino F, Kueng S, Robinson P, Tsai Pflugfelder M, van Leeuwen F, Ziegler M, et al. Reconstitution of yeast silent chromatin: multiple contact sites and O-AADPR binding load SIR complexes onto nucleosomes in vitro. Mol Cell. 2009;33:323-34 pubmed publisher
    ..The binding of Sir3 to nucleosomes is sensitive to histone H4 N-terminal tail removal, while that of Sir2-4 is not...
  49. Kurumizaka H, Wolffe A. Sin mutations of histone H3: influence on nucleosome core structure and function. Mol Cell Biol. 1997;17:6953-69 pubmed
  50. Poveda A, Pamblanco M, Tafrov S, Tordera V, Sternglanz R, Sendra R. Hif1 is a component of yeast histone acetyltransferase B, a complex mainly localized in the nucleus. J Biol Chem. 2004;279:16033-43 pubmed
    ..The enzyme specifically acetylates lysine 12, and to a lesser extent lysine 5, of free, non-chromatin-bound histone H4. The complex is usually isolated with cytosolic fractions and is thought to be involved in chromatin assembly...
  51. Dai J, Hyland E, Yuan D, Huang H, Bader J, Boeke J. Probing nucleosome function: a highly versatile library of synthetic histone H3 and H4 mutants. Cell. 2008;134:1066-78 pubmed publisher
  52. Harata M, Oma Y, Mizuno S, Jiang Y, Stillman D, Wintersberger U. The nuclear actin-related protein of Saccharomyces cerevisiae, Act3p/Arp4, interacts with core histones. Mol Biol Cell. 1999;10:2595-605 pubmed
    ..We also show that a conditional act3 mutation affects chromatin structure of an episomal DNA molecule, indicating that the putative Act3p complex may be involved in the establishment, remodeling, or maintenance of chromatin structures. ..
  53. 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
    ..the subunit yeast homolog of mammalian Ing1 2 (Yng2) apparently positions Piccolo for efficient acetylation of histone H4 or histone H2A tails...
  54. Chen J, Miller A, Kirchmaier A, Irudayaraj J. Single-molecule tools elucidate H2A.Z nucleosome composition. J Cell Sci. 2012;125:2954-64 pubmed publisher
  55. Chavez M, Scorgie J, Dennehey B, Noone S, Tyler J, Churchill M. The conformational flexibility of the C-terminus of histone H4 promotes histone octamer and nucleosome stability and yeast viability. Epigenetics Chromatin. 2012;5:5 pubmed publisher
    ..To investigate the functional consequence of this structural change in histone H4, we restricted the available conformations of the H4 C-terminus and analyzed its effect in vitro and in vivo in ..