H4C1 acetyl K16

Function

Core 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.

Involvement in disease

Tessadori-Bicknell-Van Haaften neurodevelopmental syndrome 1

TEBIVANED1

An autosomal dominant disorder with onset in infancy, characterized by poor overall growth, microcephaly, hypotonia, profound global developmental delay, impaired intellectual development, poor or absent speech, and characteristic dysmorphic facial features, including hypertelorism and abnormal nose. Other variable neurologic and systemic features may also occur.

None

The disease is caused by variants affecting the gene represented in this entry. TEBIVANED1 is caused by variants in H4C3.

Tessadori-Bicknell-Van Haaften neurodevelopmental syndrome 2

TEBIVANED2

An autosomal dominant disorder characterized by poor overall growth, microcephaly, hypotonia, profound global developmental delay, impaired intellectual development, absent speech, and characteristic dysmorphic facial features, including hypertelorism, abnormal nose, and wide mouth.

None

The disease is caused by variants affecting the gene represented in this entry. TEBIVANED2 is caused by variants in H4C11.

Tessadori-Bicknell-Van Haaften neurodevelopmental syndrome 3

TEBIVANED3

An autosomal dominant disorder characterized by global developmental delay with poor overall growth, impaired intellectual development, and speech difficulties. More variable features include hypotonia, microcephaly, and dysmorphic facies.

None

The disease is caused by variants affecting the gene represented in this entry. TEBIVANED3 is caused by variants in H4C5.

Tessadori-Bicknell-Van Haaften neurodevelopmental syndrome 4

TEBIVANED4

An autosomal dominant disorder characterized by global developmental delay with poor overall growth, variably impaired intellectual development, learning difficulties, distal skeletal anomalies, and dysmorphic facies. Some patients have visual or hearing deficits.

None

The disease is caused by variants affecting the gene represented in this entry. TEBIVANED4 is caused by variants in H4C9.

Chromosomal aberrations involving HISTONE H4 is a cause of B-cell non-Hodgkin lymphomas (B-cell NHL). Translocation t(3;6)(q27;p21), with BCL6.

Post-translational modifications

Acetylation at Lys-6 (H4K5ac), Lys-9 (H4K8ac), Lys-13 (H4K12ac) and Lys-17 (H4K16ac) occurs in coding regions of the genome but not in heterochromatin.

Citrullination at Arg-4 (H4R3ci) by PADI4 impairs methylation.

Monomethylation and asymmetric dimethylation at Arg-4 (H4R3me1 and H4R3me2a, respectively) by PRMT1 favors acetylation at Lys-9 (H4K8ac) and Lys-13 (H4K12ac). Demethylation is performed by JMJD6. Symmetric dimethylation on Arg-4 (H4R3me2s) by the PRDM1/PRMT5 complex may play a crucial role in the germ-cell lineage.

Monomethylated, dimethylated or trimethylated at Lys-21 (H4K20me1, H4K20me2, H4K20me3) (PubMed:12086618, PubMed:15964846, PubMed:17967882). Monomethylation is performed by KMT5A/SET8 (PubMed:15964846). Dimethylation and trimethylation is performed by KMT5B and KMT5C and induces gene silencing (By similarity). Monomethylated at Lys-13 (H4K12me1) by N6AMT1; H4K12me1 modification is present at the promoters of numerous genes encoding cell cycle regulators (PubMed:31061526).

Acetyl-methylated at Lys-6 and Lys-13 (H4K5acme and H4K12acme, respectively), acetyl-methylation is an epigenetic mark of active chromatin associated with increased transcriptional initiation (PubMed:37731000). Acetyl-methylation is formed by acetylation by EP300/p300 of lysine residues that are already monomethylated on the same side chain (PubMed:37731000). H4K5acme and H4K12acme marks specifically bind BRD2 (PubMed:37731000).

Phosphorylated by PAK2 at Ser-48 (H4S47ph). This phosphorylation increases the association of H3.3-H4 with the histone chaperone HIRA, thus promoting nucleosome assembly of H3.3-H4 and inhibiting nucleosome assembly of H3.1-H4.

Ubiquitinated by the CUL4-DDB-RBX1 complex in response to ultraviolet irradiation. This may weaken the interaction between histones and DNA and facilitate DNA accessibility to repair proteins. Monoubiquitinated at Lys-92 of histone H4 (H4K91ub1) in response to DNA damage. The exact role of H4K91ub1 in DNA damage response is still unclear but it may function as a licensing signal for additional histone H4 post-translational modifications such as H4 Lys-21 methylation (H4K20me).

Ufmylated; monofmylated by UFL1 at Lys-32 (H4K31Ufm1) in response to DNA damage.

Sumoylated, which is associated with transcriptional repression.

Crotonylation (Kcr) is specifically present in male germ cells and marks testis-specific genes in post-meiotic cells, including X-linked genes that escape sex chromosome inactivation in haploid cells. Crotonylation marks active promoters and enhancers and confers resistance to transcriptional repressors. It is also associated with post-meiotically activated genes on autosomes.

Butyrylation of histones marks active promoters and competes with histone acetylation.

Glutarylation at Lys-92 (H4K91glu) destabilizes nucleosomes by promoting dissociation of the H2A-H2B dimers from nucleosomes.

Lactylated in macrophages by EP300/P300 by using lactoyl-CoA directly derived from endogenous or exogenous lactate, leading to stimulates gene transcription.

Sequence similarities

Belongs to the histone H4 family.

Cellular localization

• Nucleus
• Chromosome

Alternative names

• Histone H4
• H4FC
• HIST1H4F
• H4C8
• H4/H
• H4FH
• HIST1H4H
• H4C9
• H4/M
• H4FM
• HIST1H4I
• H4FG
• H4C11
• H4/C
• H4C6
• HIST1H4E
• H4FJ
• H4/J
• H4C5
• HIST1H4D
• H4FB
• H4/B
• H4C4
• HIST1H4C
• H4/N
• HIST4H4
• H4-16
• H4C16
• HIST2H4B
• H4FO
• H4/O
• H4C15
• HIST2H4A
• HIST2H4
• H4FN
• H4F2
• H4/E
• H4C14
• HIST1H4L
• H4FK
• H4/K
• H4C13
• HIST1H4K
• H4FD
• H4/D
• H4C12
• HIST1H4J
• H4FE
• H4C3
• H4/G
• H4C1
• H4/A
• H4FA
• HIST1H4A
• H4C2
• H4/I
• H4FI
• HIST1H4B
• H4K16ac

Database links

• swissprot:P62805

Target type

Proteins

Molecular weight

11367Da