Histone H4

NameHistone H4
Synonyms
  • H4/A
  • H4/B
  • H4/C
  • H4/D
  • H4/E
  • H4/G
  • H4/H
  • H4/I
  • H4/J
  • H4/K
  • H4/M
  • H4/N
  • H4/O
  • H4F2
  • H4FA
  • H4FB
  • H4FC
  • H4FD
  • H4FE
  • H4FG
  • H4FH
  • H4FI
  • H4FJ
  • H4FK
  • H4FM
  • H4FN
  • H4FO
  • HIST2H4
Gene NameHIST1H4A
OrganismHuman
Amino acid sequence
>lcl|BSEQ0008763|Histone H4
MSGRGKGGKGLGKGGAKRHRKVLRDNIQGITKPAIRRLARRGGVKRISGLIYEETRGVLK
VFLENVIRDAVTYTEHAKRKTVTAMDVVYALKRQGRTLYGFGG
Number of residues103
Molecular Weight11367.3
Theoretical pINot Available
GO Classification
Functions
  • poly(A) RNA binding
  • histone binding
  • DNA binding
  • protein domain specific binding
  • histone demethylase activity (H4-K20 specific)
Processes
  • protein heterotetramerization
  • CENP-A containing nucleosome assembly
  • DNA replication-dependent nucleosome assembly
  • histone H4-K20 demethylation
  • DNA methylation on cytosine
  • negative regulation of gene expression, epigenetic
  • DNA repair
  • regulation of gene expression, epigenetic
  • small GTPase mediated signal transduction
  • gene expression
  • negative regulation of megakaryocyte differentiation
  • chromatin organization
  • gene silencing by RNA
  • double-strand break repair
  • double-strand break repair via homologous recombination
  • cellular protein metabolic process
  • chromatin silencing at rDNA
  • mitotic cell cycle
  • DNA replication-independent nucleosome assembly
  • double-strand break repair via nonhomologous end joining
  • nucleosome assembly
  • telomere maintenance
Components
  • protein complex
  • extracellular region
  • nucleus
  • nuclear chromosome, telomeric region
  • extracellular exosome
  • nucleoplasm
  • nuclear chromosome
  • nucleosome
  • membrane
General FunctionProtein domain specific binding
Specific FunctionCore component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.
Pfam Domain FunctionNot Available
Transmembrane RegionsNot Available
GenBank Protein IDNot Available
UniProtKB IDP62805
UniProtKB Entry NameH4_HUMAN
Cellular LocationNucleus
Gene sequence
>lcl|BSEQ0013402|Histone H4 (HIST1H4A)
ATGTCTGGGCGAGGTAAAGGTGGCAAGGGGCTGGGTAAGGGAGGCGCCAAGCGCCACCGG
AAGGTGCTGCGGGACAATATCCAAGGCATTACAAAGCCGGCGATTCGCCGTCTCGCCCGA
CGTGGGGGCGTCAAGCGCATTTCTGGTCTCATCTACGAGGAGACCCGGGGAGTCCTCAAA
GTCTTCCTGGAGAACGTGATCCGTGACGCGGTGACTTACACGGAGCACGCCAAGCGCAAG
ACCGTCACGGCCATGGATGTGGTGTACGCGCTGAAACGCCAGGGTCGCACCCTTTATGGT
TTCGGCGGTTGA
GenBank Gene IDNot Available
GeneCard IDNot Available
GenAtlas IDNot Available
HGNC IDHGNC:4781
Chromosome Location1
LocusNot Available
References
  1. Sierra F, Stein G, Stein J: Structure and in vitro transcription of a human H4 histone gene. Nucleic Acids Res. 1983 Oct 25;11(20):7069-86. 6314274
  2. Pauli U, Chrysogelos S, Stein G, Stein J, Nick H: Protein-DNA interactions in vivo upstream of a cell cycle-regulated human H4 histone gene. Science. 1987 Jun 5;236(4806):1308-11. 3035717
  3. Albig W, Kardalinou E, Drabent B, Zimmer A, Doenecke D: Isolation and characterization of two human H1 histone genes within clusters of core histone genes. Genomics. 1991 Aug;10(4):940-8. 1916825
  4. Drabent B, Kardalinou E, Bode C, Doenecke D: Association of histone H4 genes with the mammalian testis-specific H1t histone gene. DNA Cell Biol. 1995 Jul;14(7):591-7. 7626218
  5. Albig W, Meergans T, Doenecke D: Characterization of the H1.5 gene completes the set of human H1 subtype genes. Gene. 1997 Jan 15;184(2):141-8. 9031620
  6. Albig W, Doenecke D: The human histone gene cluster at the D6S105 locus. Hum Genet. 1997 Dec;101(3):284-94. 9439656
  7. Albig W, Kioschis P, Poustka A, Meergans K, Doenecke D: Human histone gene organization: nonregular arrangement within a large cluster. Genomics. 1997 Mar 1;40(2):314-22. 9119399
  8. Marzluff WF, Gongidi P, Woods KR, Jin J, Maltais LJ: The human and mouse replication-dependent histone genes. Genomics. 2002 Nov;80(5):487-98. 12408966
  9. Akasaka T, Miura I, Takahashi N, Akasaka H, Yonetani N, Ohno H, Fukuhara S, Okuma M: A recurring translocation, t(3;6)(q27;p21), in non-Hodgkin's lymphoma results in replacement of the 5' regulatory region of BCL6 with a novel H4 histone gene. Cancer Res. 1997 Jan 1;57(1):7-12. 8988030
  10. Braastad CD, Hovhannisyan H, van Wijnen AJ, Stein JL, Stein GS: Functional characterization of a human histone gene cluster duplication. Gene. 2004 Nov 10;342(1):35-40. 15527963
  11. Mungall AJ, Palmer SA, Sims SK, Edwards CA, Ashurst JL, Wilming L, Jones MC, Horton R, Hunt SE, Scott CE, Gilbert JG, Clamp ME, Bethel G, Milne S, Ainscough R, Almeida JP, Ambrose KD, Andrews TD, Ashwell RI, Babbage AK, Bagguley CL, Bailey J, Banerjee R, Barker DJ, Barlow KF, Bates K, Beare DM, Beasley H, Beasley O, Bird CP, Blakey S, Bray-Allen S, Brook J, Brown AJ, Brown JY, Burford DC, Burrill W, Burton J, Carder C, Carter NP, Chapman JC, Clark SY, Clark G, Clee CM, Clegg S, Cobley V, Collier RE, Collins JE, Colman LK, Corby NR, Coville GJ, Culley KM, Dhami P, Davies J, Dunn M, Earthrowl ME, Ellington AE, Evans KA, Faulkner L, Francis MD, Frankish A, Frankland J, French L, Garner P, Garnett J, Ghori MJ, Gilby LM, Gillson CJ, Glithero RJ, Grafham DV, Grant M, Gribble S, Griffiths C, Griffiths M, Hall R, Halls KS, Hammond S, Harley JL, Hart EA, Heath PD, Heathcott R, Holmes SJ, Howden PJ, Howe KL, Howell GR, Huckle E, Humphray SJ, Humphries MD, Hunt AR, Johnson CM, Joy AA, Kay M, Keenan SJ, Kimberley AM, King A, Laird GK, Langford C, Lawlor S, Leongamornlert DA, Leversha M, Lloyd CR, Lloyd DM, Loveland JE, Lovell J, Martin S, Mashreghi-Mohammadi M, Maslen GL, Matthews L, McCann OT, McLaren SJ, McLay K, McMurray A, Moore MJ, Mullikin JC, Niblett D, Nickerson T, Novik KL, Oliver K, Overton-Larty EK, Parker A, Patel R, Pearce AV, Peck AI, Phillimore B, Phillips S, Plumb RW, Porter KM, Ramsey Y, Ranby SA, Rice CM, Ross MT, Searle SM, Sehra HK, Sheridan E, Skuce CD, Smith S, Smith M, Spraggon L, Squares SL, Steward CA, Sycamore N, Tamlyn-Hall G, Tester J, Theaker AJ, Thomas DW, Thorpe A, Tracey A, Tromans A, Tubby B, Wall M, Wallis JM, West AP, White SS, Whitehead SL, Whittaker H, Wild A, Willey DJ, Wilmer TE, Wood JM, Wray PW, Wyatt JC, Young L, Younger RM, Bentley DR, Coulson A, Durbin R, Hubbard T, Sulston JE, Dunham I, Rogers J, Beck S: The DNA sequence and analysis of human chromosome 6. Nature. 2003 Oct 23;425(6960):805-11. 14574404
  12. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. 15489334
  13. O'Neill LP, Turner BM: Histone H4 acetylation distinguishes coding regions of the human genome from heterochromatin in a differentiation-dependent but transcription-independent manner. EMBO J. 1995 Aug 15;14(16):3946-57. 7664735
  14. Ebralidse KK, Grachev SA, Mirzabekov AD: A highly basic histone H4 domain bound to the sharply bent region of nucleosomal DNA. Nature. 1988 Jan 28;331(6154):365-7. 3340182
  15. Turner BM, O'Neill LP, Allan IM: Histone H4 acetylation in human cells. Frequency of acetylation at different sites defined by immunolabeling with site-specific antibodies. FEBS Lett. 1989 Aug 14;253(1-2):141-5. 2474456
  16. Strahl BD, Briggs SD, Brame CJ, Caldwell JA, Koh SS, Ma H, Cook RG, Shabanowitz J, Hunt DF, Stallcup MR, Allis CD: Methylation of histone H4 at arginine 3 occurs in vivo and is mediated by the nuclear receptor coactivator PRMT1. Curr Biol. 2001 Jun 26;11(12):996-1000. 11448779
  17. Wang H, Huang ZQ, Xia L, Feng Q, Erdjument-Bromage H, Strahl BD, Briggs SD, Allis CD, Wong J, Tempst P, Zhang Y: Methylation of histone H4 at arginine 3 facilitating transcriptional activation by nuclear hormone receptor. Science. 2001 Aug 3;293(5531):853-7. Epub 2001 May 31. 11387442
  18. Kurata M, Maesako Y, Ueda C, Nishikori M, Akasaka T, Uchiyama T, Ohno H: Characterization of t(3;6)(q27;p21) breakpoints in B-cell non-Hodgkin's lymphoma and construction of the histone H4/BCL6 fusion gene, leading to altered expression of Bcl-6. Cancer Res. 2002 Nov 1;62(21):6224-30. 12414651
  19. Nishioka K, Rice JC, Sarma K, Erdjument-Bromage H, Werner J, Wang Y, Chuikov S, Valenzuela P, Tempst P, Steward R, Lis JT, Allis CD, Reinberg D: PR-Set7 is a nucleosome-specific methyltransferase that modifies lysine 20 of histone H4 and is associated with silent chromatin. Mol Cell. 2002 Jun;9(6):1201-13. 12086618
  20. Shiio Y, Eisenman RN: Histone sumoylation is associated with transcriptional repression. Proc Natl Acad Sci U S A. 2003 Nov 11;100(23):13225-30. Epub 2003 Oct 24. 14578449
  21. Wang Y, Wysocka J, Sayegh J, Lee YH, Perlin JR, Leonelli L, Sonbuchner LS, McDonald CH, Cook RG, Dou Y, Roeder RG, Clarke S, Stallcup MR, Allis CD, Coonrod SA: Human PAD4 regulates histone arginine methylation levels via demethylimination. Science. 2004 Oct 8;306(5694):279-83. Epub 2004 Sep 2. 15345777
  22. Yin Y, Liu C, Tsai SN, Zhou B, Ngai SM, Zhu G: SET8 recognizes the sequence RHRK20VLRDN within the N terminus of histone H4 and mono-methylates lysine 20. J Biol Chem. 2005 Aug 26;280(34):30025-31. Epub 2005 Jun 17. 15964846
  23. Rush J, Moritz A, Lee KA, Guo A, Goss VL, Spek EJ, Zhang H, Zha XM, Polakiewicz RD, Comb MJ: Immunoaffinity profiling of tyrosine phosphorylation in cancer cells. Nat Biotechnol. 2005 Jan;23(1):94-101. Epub 2004 Dec 12. 15592455
  24. Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, Mann M: Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. Cell. 2006 Nov 3;127(3):635-48. 17081983
  25. Wang H, Zhai L, Xu J, Joo HY, Jackson S, Erdjument-Bromage H, Tempst P, Xiong Y, Zhang Y: Histone H3 and H4 ubiquitylation by the CUL4-DDB-ROC1 ubiquitin ligase facilitates cellular response to DNA damage. Mol Cell. 2006 May 5;22(3):383-94. 16678110
  26. Arita K, Shimizu T, Hashimoto H, Hidaka Y, Yamada M, Sato M: Structural basis for histone N-terminal recognition by human peptidylarginine deiminase 4. Proc Natl Acad Sci U S A. 2006 Apr 4;103(14):5291-6. Epub 2006 Mar 27. 16567635
  27. Pesavento JJ, Yang H, Kelleher NL, Mizzen CA: Certain and progressive methylation of histone H4 at lysine 20 during the cell cycle. Mol Cell Biol. 2008 Jan;28(1):468-86. Epub 2007 Oct 29. 17967882
  28. Dephoure N, Zhou C, Villen J, Beausoleil SA, Bakalarski CE, Elledge SJ, Gygi SP: A quantitative atlas of mitotic phosphorylation. Proc Natl Acad Sci U S A. 2008 Aug 5;105(31):10762-7. doi: 10.1073/pnas.0805139105. Epub 2008 Jul 31. 18669648
  29. Yan Q, Dutt S, Xu R, Graves K, Juszczynski P, Manis JP, Shipp MA: BBAP monoubiquitylates histone H4 at lysine 91 and selectively modulates the DNA damage response. Mol Cell. 2009 Oct 9;36(1):110-20. doi: 10.1016/j.molcel.2009.08.019. 19818714
  30. Mayya V, Lundgren DH, Hwang SI, Rezaul K, Wu L, Eng JK, Rodionov V, Han DK: Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions. Sci Signal. 2009 Aug 18;2(84):ra46. doi: 10.1126/scisignal.2000007. 19690332
  31. Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M: Lysine acetylation targets protein complexes and co-regulates major cellular functions. Science. 2009 Aug 14;325(5942):834-40. doi: 10.1126/science.1175371. Epub 2009 Jul 16. 19608861
  32. Olsen JV, Vermeulen M, Santamaria A, Kumar C, Miller ML, Jensen LJ, Gnad F, Cox J, Jensen TS, Nigg EA, Brunak S, Mann M: Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis. Sci Signal. 2010 Jan 12;3(104):ra3. doi: 10.1126/scisignal.2000475. 20068231
  33. Burkard TR, Planyavsky M, Kaupe I, Breitwieser FP, Burckstummer T, Bennett KL, Superti-Furga G, Colinge J: Initial characterization of the human central proteome. BMC Syst Biol. 2011 Jan 26;5:17. doi: 10.1186/1752-0509-5-17. 21269460
  34. Tan M, Luo H, Lee S, Jin F, Yang JS, Montellier E, Buchou T, Cheng Z, Rousseaux S, Rajagopal N, Lu Z, Ye Z, Zhu Q, Wysocka J, Ye Y, Khochbin S, Ren B, Zhao Y: Identification of 67 histone marks and histone lysine crotonylation as a new type of histone modification. Cell. 2011 Sep 16;146(6):1016-28. doi: 10.1016/j.cell.2011.08.008. 21925322
  35. Kang B, Pu M, Hu G, Wen W, Dong Z, Zhao K, Stillman B, Zhang Z: Phosphorylation of H4 Ser 47 promotes HIRA-mediated nucleosome assembly. Genes Dev. 2011 Jul 1;25(13):1359-64. doi: 10.1101/gad.2055511. 21724829
  36. Rigbolt KT, Prokhorova TA, Akimov V, Henningsen J, Johansen PT, Kratchmarova I, Kassem M, Mann M, Olsen JV, Blagoev B: System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation. Sci Signal. 2011 Mar 15;4(164):rs3. doi: 10.1126/scisignal.2001570. 21406692
  37. Bian Y, Song C, Cheng K, Dong M, Wang F, Huang J, Sun D, Wang L, Ye M, Zou H: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J Proteomics. 2014 Jan 16;96:253-62. doi: 10.1016/j.jprot.2013.11.014. Epub 2013 Nov 22. 24275569
  38. Hendriks IA, D'Souza RC, Yang B, Verlaan-de Vries M, Mann M, Vertegaal AC: Uncovering global SUMOylation signaling networks in a site-specific manner. Nat Struct Mol Biol. 2014 Oct;21(10):927-36. doi: 10.1038/nsmb.2890. Epub 2014 Sep 14. 25218447
  39. Vaca Jacome AS, Rabilloud T, Schaeffer-Reiss C, Rompais M, Ayoub D, Lane L, Bairoch A, Van Dorsselaer A, Carapito C: N-terminome analysis of the human mitochondrial proteome. Proteomics. 2015 Jul;15(14):2519-24. doi: 10.1002/pmic.201400617. Epub 2015 Jun 8. 25944712
  40. Tsunaka Y, Kajimura N, Tate S, Morikawa K: Alteration of the nucleosomal DNA path in the crystal structure of a human nucleosome core particle. Nucleic Acids Res. 2005 Jun 10;33(10):3424-34. Print 2005. 15951514
  41. Sjoblom T, Jones S, Wood LD, Parsons DW, Lin J, Barber TD, Mandelker D, Leary RJ, Ptak J, Silliman N, Szabo S, Buckhaults P, Farrell C, Meeh P, Markowitz SD, Willis J, Dawson D, Willson JK, Gazdar AF, Hartigan J, Wu L, Liu C, Parmigiani G, Park BH, Bachman KE, Papadopoulos N, Vogelstein B, Kinzler KW, Velculescu VE: The consensus coding sequences of human breast and colorectal cancers. Science. 2006 Oct 13;314(5797):268-74. Epub 2006 Sep 7. 16959974