H4

Histone H4

• SMART accession number: SM00417
• Description: -
• Interpro abstract (IPR001951):

  Histone H4 is one of the five histones, along with H1/H5, H2A, H2B and H3. Two copies of each of the H2A, H2B, H3, and H4 histones ensemble to form the core of the nucleosome [ (PUBMED:16472024) ]. The nucleosome forms octameric structure that wraps DNA in a left-handed manner. H3 is a highly conserved protein of 135 amino acid residues [ (PUBMED:8121801) (PUBMED:2041803) ]. Histones can undergo several different types of post-translational modifications that affect transcription, DNA repair, DNA replication and chromosomal stability. The sequence of histone H4 has remained almost invariant in more then 2 billion years of evolution [ (PUBMED:8121801) (PUBMED:6808351) (PUBMED:3340182) ].

• GO function: DNA binding (GO:0003677)

There are 2776 H4 domains in 2524 proteins in SMART's nrdb database.

Literature (relevant references for this domain)

Primary literature is listed below; Automatically-derived, secondary literature is also avaliable.

• Luger K, Richmond TJ
• DNA binding within the nucleosome core.
• Curr Opin Struct Biol. 1998; 8: 33-40

The high resolution structure of the nucleosome core particle of chromatin reveals the form of DNA that is predominant in living cells and offers a wealth of information on DNA binding and bending by the histone octamer. Recent studies imply that chromatin is highly dynamic. This propensity for unfolding and refolding stems from the structural design of the nucleosome core. The histone-fold motif, central to nucleosome structure, is also found in other proteins involved in transcriptional regulation.

• Burley SK, Xie X, Clark KL, Shu F
• Histone-like transcription factors in eukaryotes.
• Curr Opin Struct Biol. 1997; 7: 94-102

Histone proteins have long been recognized as important regulators of eukaryotic gene expression. Condensation of DNA into chromatin by the core (H2A, H2B, H3, H4) and linker (H1, H5) histones effectively represses transcription initiation from the promoters of genes that have been packaged. Recently, eukaryotic transcriptional activators and coactivators (both positive and negative) resembling core and linker histone proteins have been discovered. Substantial progress has been made on structural and mechanistic studies of histones and histone-like transcription factors. Three-dimensional structures solved include the core histone octamer, an archael histone homodimer, two core histone-like subunits of transcription factor IID, a linker histone, and a linker histone-like transcriptional activator.

• Luger K, Mader AW, Richmond RK, Sargent DF, Richmond TJ
• Crystal structure of the nucleosome core particle at 2.8 A resolution.
• Nature. 1997; 389: 251-60

The X-ray crystal structure of the nucleosome core particle of chromatin shows in atomic detail how the histone protein octamer is assembled and how 146 base pairs of DNA are organized into a superhelix around it. Both histone/histone and histone/DNA interactions depend on the histone fold domains and additional, well ordered structure elements extending from this motif. Histone amino-terminal tails pass over and between the gyres of the DNA superhelix to contact neighbouring particles. The lack of uniformity between multiple histone/DNA-binding sites causes the DNA to deviate from ideal superhelix geometry.

• Thatcher TH, Gorovsky MA
• Phylogenetic analysis of the core histones H2A, H2B, H3, and H4.
• Nucleic Acids Res. 1994; 22: 174-9

Despite the ubiquity of histones in eukaryotes and their important role in determining the structure and function of chromatin, no detailed studies of the evolution of the histones have been reported. We have constructed phylogenetic trees for the core histones H2A, H2B, H3, and H4. Histones which form dimers (H2A/H2B and H3/H4) have very similar trees and appear to have co-evolved, with the exception of the divergent sea urchin testis H2Bs, for which no corresponding divergent H2As have been identified. The trees for H2A and H2B also support the theory that animals and fungi have a common ancestor. H3 and H4 are 10-fold less divergent than H2A and H2B. Three evolutionary histories are observed for histone variants. H2A.F/Z-type variants arose once early in evolution, while H2A.X variants arose separately, during the evolution of multicellular animals. H3.3-type variants have arisen in multiple independent events.

• Ebralidse KK, Grachev SA, Mirzabekov AD
• A highly basic histone H4 domain bound to the sharply bent region of nucleosomal DNA.
• Nature. 1988; 331: 365-7

A nucleosomal core particle is composed of two each of histones H2A, H2B, H3 and H4 located inside the particle with approximately 47 base pairs (bp) of DNA wrapped around the octamer in about 1.8 turns of a left-handed superhelix. The path of the superhelix is not smooth; the DNA is sharply bent, or kinked, at positions symmetrically disposed at a distance of about one and four double-helical turns in both directions from the nucleosomal dyad axis (designated as sites +/- 1 and +/- 4 respectively). This non-uniform bending is considered archetypal to other DNA-protein complexes, but its mechanism is not clear (reviewed in ref. 4). DNA-histone chemical cross-linking within the core particle has revealed strong binding of each of the two histone H4 molecules to DNA at a distance of 1.5 helical turns either side of the nucleosomal dyad axis (sites +/- 1.5). In each of these sites, a single flexible domain of H4 was previously shown to contact three points, at about nucleotides 55 and 65 on one strand and nucleotide 88 on the complementary strand, numbering from the 5' terminus of each 147-base strand; these three locations are closely juxtaposed across the highly compressed minor and major grooves (Fig. 1). Here we report that the amino-acid residue of histone H4 cross-linked at the 1.5 site is histidine-18, embedded in a highly basic cluster Lys-Arg-His-Arg-Lys-Val-Leu-Arg which is probably involved in the sharp bending of the DNA double helix at the +/- 1 sites.

Structure (3D structures containing this domain)

3D Structures of H4 domains in PDB

PDB code	Title
1aoi	COMPLEX BETWEEN NUCLEOSOME CORE PARTICLE (H3,H4,H2A,H2B) AND 146 BP LONG DNA FRAGMENT
1eqz	X-RAY STRUCTURE OF THE NUCLEOSOME CORE PARTICLE AT 2.5 A RESOLUTION
1f66	2.6 A CRYSTAL STRUCTURE OF A NUCLEOSOME CORE PARTICLE CONTAINING THE VARIANT HISTONE H2A.Z
1hio	HISTONE OCTAMER (CHICKEN), CHROMOSOMAL PROTEIN, ALPHA CARBONS ONLY
1hq3	CRYSTAL STRUCTURE OF THE HISTONE-CORE-OCTAMER IN KCL/PHOSPHATE
1id3	CRYSTAL STRUCTURE OF THE YEAST NUCLEOSOME CORE PARTICLE REVEALS FUNDAMENTAL DIFFERENCES IN INTER-NUCLEOSOME INTERACTIONS
1kx3	X-Ray Structure of the Nucleosome Core Particle, NCP146, at 2.0 A Resolution
1kx4	X-Ray Structure of the Nucleosome Core Particle, NCP146b, at 2.6 A Resolution
1kx5	X-Ray Structure of the Nucleosome Core Particle, NCP147, at 1.9 A Resolution
1m18	LIGAND BINDING ALTERS THE STRUCTURE AND DYNAMICS OF NUCLEOSOMAL DNA
1m19	LIGAND BINDING ALTERS THE STRUCTURE AND DYNAMICS OF NUCLEOSOMAL DNA
1m1a	LIGAND BINDING ALTERS THE STRUCTURE AND DYNAMICS OF NUCLEOSOMAL DNA
1p34	Crystallographic Studies of Nucleosome Core Particles containing Histone 'Sin' Mutants
1p3a	Crystallographic Studies of Nucleosome Core Particles containing Histone 'Sin' Mutants
1p3b	Crystallographic Studies of Nucleosome Core Particles containing Histone 'Sin' Mutants
1p3f	Crystallographic Studies of Nucleosome Core Particles containing Histone 'Sin' Mutants
1p3g	Crystallographic Studies of Nucleosome Core Particles containing Histone 'Sin' Mutants
1p3i	Crystallographic Studies of Nucleosome Core Particles containing Histone 'Sin' Mutants
1p3k	Crystallographic Studies of Nucleosome Core Particles containing Histone 'Sin' Mutants
1p3l	Crystallographic Studies of Nucleosome Core Particles containing Histone 'Sin' Mutants
1p3m	Crystallographic Studies of Nucleosome Core Particles containing Histone 'Sin' Mutants
1p3o	Crystallographic Studies of Nucleosome Core Particles containing Histone 'Sin' Mutants
1p3p	Crystallographic Studies of Nucleosome Core Particles containing Histone 'Sin' Mutants
1s32	Molecular Recognition of the Nucleosomal 'Supergroove'
1tzy	Crystal Structure of the Core-Histone Octamer to 1.90 Angstrom Resolution
1u35	Crystal structure of the nucleosome core particle containing the histone domain of macroH2A
1zbb	Structure of the 4_601_167 Tetranucleosome
1zla	X-ray Structure of a Kaposi's sarcoma herpesvirus LANA peptide bound to the nucleosomal core
2aro	Crystal Structure Of The Native Histone Octamer To 2.1 Angstrom Resolution, Crystalised In The Presence Of S-Nitrosoglutathione
2cv5	Crystal structure of human nucleosome core particle
2f8n	2.9 Angstrom X-ray structure of hybrid macroH2A nucleosomes
2fj7	Crystal structure of Nucleosome Core Particle Containing a Poly (dA.dT) Sequence Element
2hio	HISTONE OCTAMER (CHICKEN), CHROMOSOMAL PROTEIN
2hue	Structure of the H3-H4 chaperone Asf1 bound to histones H3 and H4
2io5	Crystal structure of the CIA- histone H3-H4 complex
2l5a	Structural basis for recognition of centromere specific histone H3 variant by nonhistone Scm3
2ly8	The budding yeast chaperone Scm3 recognizes the partially unfolded dimer of the centromere-specific Cse4/H4 histone variant
2nqb	Drosophila Nucleosome Structure
2nzd	Nucleosome core particle containing 145 bp of DNA
2pyo	Drosophila nucleosome core
2yfv	The heterotrimeric complex of Kluyveromyces lactis Scm3, Cse4 and H4
2yfw	Heterotetramer structure of Kluyveromyces lactis Cse4,H4
3a6n	The nucleosome containing a testis-specific histone variant, human H3T
3afa	The human nucleosome structure
3an2	The structure of the centromeric nucleosome containing CENP-A
3av1	The human nucleosome structure containing the histone variant H3.2
3av2	The human nucleosome structure containing the histone variant H3.3
3ayw	Crystal Structure of Human Nucleosome Core Particle Containing H3K56Q mutation
3aze	Crystal Structure of Human Nucleosome Core Particle Containing H3K64Q mutation
3azf	Crystal Structure of Human Nucleosome Core Particle Containing H3K79Q mutation
3azg	Crystal Structure of Human Nucleosome Core Particle Containing H3K115Q mutation
3azh	Crystal Structure of Human Nucleosome Core Particle Containing H3K122Q mutation
3azi	Crystal Structure of Human Nucleosome Core Particle Containing H4K31Q mutation
3azj	Crystal Structure of Human Nucleosome Core Particle Containing H4K44Q mutation
3azk	Crystal Structure of Human Nucleosome Core Particle Containing H4K59Q mutation
3azl	Crystal Structure of Human Nucleosome Core Particle Containing H4K77Q mutation
3azm	Crystal Structure of Human Nucleosome Core Particle Containing H4K79Q mutation
3azn	Crystal Structure of Human Nucleosome Core Particle Containing H4K91Q mutation
3b6f	Nucleosome core particle treated with cisplatin
3b6g	Nucleosome core particle treated with oxaliplatin
3c1b	The effect of H3 K79 dimethylation and H4 K20 trimethylation on nucleosome and chromatin structure
3c1c	The effect of H3 K79 dimethylation and H4 K20 trimethylation on nucleosome and chromatin structure
3c9k	Model of Histone Octamer Tubular Crystals
3kuy	DNA Stretching in the Nucleosome Facilitates Alkylation by an Intercalating Antitumor Agent
3kwq	Structural characterization of H3K56Q nucleosomes and nucleosomal arrays
3kxb	Structural characterization of H3K56Q nucleosomes and nucleosomal arrays
3lel	Structural Insight into the Sequence-Dependence of Nucleosome Positioning
3lja	Using Soft X-Rays for a Detailed Picture of Divalent Metal Binding in the Nucleosome
3lz0	Crystal Structure of Nucleosome Core Particle Composed of the Widom 601 DNA Sequence (orientation 1)
3lz1	Crystal Structure of Nucleosome Core Particle Composed of the Widom 601 DNA Sequence (orientation 2)
3mgp	Binding of Cobalt ions to the Nucleosome Core Particle
3mgq	Binding of Nickel ions to the Nucleosome Core Particle
3mgr	Binding of Rubidium ions to the Nucleosome Core Particle
3mgs	Binding of Cesium ions to the Nucleosome Core particle
3mnn	A Ruthenium Antitumour Agent Forms Specific Histone Protein Adducts in the Nucleosome Core
3mvd	Crystal structure of the chromatin factor RCC1 in complex with the nucleosome core particle
3nqj	Crystal structure of (CENP-A/H4)2 heterotetramer
3nqu	Crystal structure of partially trypsinized (CENP-A/H4)2 heterotetramer
3o62	Nucleosome core particle modified with a cisplatin 1,3-cis-{Pt(NH3)2}2+-d(GpTpG) intrastrand cross-link
3r45	Structure of a CENP-A-Histone H4 Heterodimer in complex with chaperone HJURP
3reh	2.5 Angstrom Crystal Structure of the Nucleosome Core Particle Assembled with a 145 bp Alpha-Satellite DNA (NCP145)
3rei	2.65 Angstrom Crystal Structure of the Nucleosome Core Particle Assembled with a 145 bp Alpha-Satellite DNA (NCP145) Derivatized with Triamminechloroplatinum(II) Chloride
3rej	2.55 Angstrom Crystal Structure of the Nucleosome Core Particle Assembled with a 146 bp Alpha-Satellite DNA (NCP146b)
3rek	2.6 Angstrom Crystal Structure of the Nucleosome Core Particle Assembled with a 146 bp Alpha-Satellite DNA (NCP146b) Derivatized with Oxaliplatin
3rel	2.7 Angstrom Crystal Structure of the Nucleosome Core Particle Assembled with a 146 bp Alpha-Satellite DNA (NCP146b) Derivatized with Triamminechloroplatinum(II) Chloride
3tu4	Crystal structure of the Sir3 BAH domain in complex with a nucleosome core particle.
3ut9	Crystal Structure of Nucleosome Core Particle Assembled with a Palindromic Widom '601' Derivative (NCP-601L)
3uta	Crystal Structure of Nucleosome Core Particle Assembled with an Alpha-Satellite Sequence Containing Two TTAAA elements (NCP-TA2)
3utb	Crystal Structure of Nucleosome Core Particle Assembled with the 146b Alpha-Satellite Sequence (NCP146b)
3w96	Crystal Structure of Human Nucleosome Core Particle lacking H2A N-terminal region
3w97	Crystal Structure of Human Nucleosome Core Particle lacking H2B N-terminal region
3w98	Crystal Structure of Human Nucleosome Core Particle lacking H3.1 N-terminal region
3w99	Crystal Structure of Human Nucleosome Core Particle lacking H4 N-terminal region
3wa9	The nucleosome containing human H2A.Z.1
3waa	The nucleosome containing human H2A.Z.2
3wkj	The nucleosome containing human TSH2B
3wtp	3WTP
3x1s	3X1S
3x1t	3X1T
3x1u	3X1U
3x1v	3X1V
4eo5	Yeast Asf1 bound to H3/H4G94P mutant
4h9n	Complex structure 1 of DAXX/H3.3(sub5)/H4
4h9o	Complex structure 2 of DAXX/H3.3(sub5,G90M)/H4
4h9p	Complex structure 3 of DAXX/H3.3(sub5,G90A)/H4
4h9q	Complex structure 4 of DAXX(E225A)/H3.3(sub5)/H4
4h9r	Complex structure 5 of DAXX(E225A)/H3.3(sub5,G90A)/H4
4h9s	Complex structure 6 of DAXX/H3.3(sub7)/H4
4hga	Structure of the variant histone H3.3-H4 heterodimer in complex with its chaperone DAXX
4j8u	X-ray structure of NCP145 with chlorido(eta-6-p-cymene)(N-phenyl-2-pyridinecarbothioamide)osmium(II)
4j8v	X-ray structure of NCP145 with bound chlorido(eta-6-p-cymene)(N-phenyl-2-pyridinecarbothioamide)ruthenium(II)
4j8w	X-ray structure of NCP145 with chlorido(eta-6-p-cymene)(N-fluorophenyl-2-pyridinecarbothioamide)osmium(II)
4j8x	X-ray structure of NCP145 with bound chlorido(eta-6-p-cymene)(N-fluorophenyl-2-pyridinecarbothioamide)ruthenium(II)
4jjn	Crystal structure of heterochromatin protein Sir3 in complex with a silenced yeast nucleosome
4kgc	Nucleosome Core Particle Containing (ETA6-P-CYMENE)-(1, 2-ETHYLENEDIAMINE)-RUTHENIUM
4kud	Crystal structure of N-terminal acetylated Sir3 BAH domain D205N mutant in complex with yeast nucleosome core particle
4ld9	Crystal structure of the N-terminally acetylated BAH domain of Sir3 bound to the nucleosome core particle
4qlc	4QLC
4r8p	4R8P
4uuz	4UUZ
4wu8	4WU8
4wu9	4WU9
4x23	4X23
4xuj	4XUJ
4xyi	4XYI
4xzq	4XZQ
4ym5	4YM5
4ym6	4YM6
4ys3	4YS3
4z2m	4Z2M
4z5t	4Z5T
4z66	4Z66
4zbj	4ZBJ
4zux	4ZUX
5av5	5AV5
5av6	5AV6
5av8	5AV8
5av9	5AV9
5avb	5AVB
5avc	5AVC
5ay8	5AY8
5b0y	5B0Y
5b0z	5B0Z
5b24	5B24
5b2i	5B2I
5b2j	5B2J
5b31	5B31
5b32	5B32
5b33	5B33
5b40	5B40
5bnv	5BNV
5bnx	5BNX
5bo0	5BO0
5bs7	5BS7
5bsa	5BSA
5c3i	5C3I
5cp6	5CP6
5cpi	5CPI
5cpj	5CPJ
5cpk	5CPK
5dnm	5DNM
5dnn	5DNN
5e5a	5E5A
5f99	5F99
5hq2	5HQ2
5ja4	5JA4
5kdm	5KDM
5kgf	5KGF

Links (links to other resources describing this domain)

• PFAM: histone
• INTERPRO: IPR001951
• PROSITE: HISTONE_H4