Epigenetics Research: Open Access
Open Access

Various Post-Translational Modifications (PTMs) of Histones

Ryan Zaiac^{* *}Correspondence: Ryan Zaiac, Department of Molecular Biology, McMaster University, Hamilton, Canada, Email:

Author info »

Description

The nucleosome, consisting of DNA wrapped around a core histone octamer, is the fundamental unit of chromatin organization. The positioning and stability of nucleosomes play a critical role in gene expression and other DNA-dependent processes. The Post-translational Modifications (PTMs) of histones, such as acetylation, methylation, phosphorylation, ubiquitination, and SUMOylation, are known to regulate nucleosome stability and positioning, and consequently, gene expression.

Histone Acetylation: Histone acetylation is the most extensively studied PTM and is known to promote gene expression. Acetylation of the lysine residues on histone tails neutralizes their positive charge, resulting in reduced affinity between DNA and histones, leading to nucleosome destabilization. Acetylated histones also recruit bromodomain-containing proteins that bind to acetylated lysines and promote chromatin remodeling and transcriptional activation. Conversely, deacetylation of histones by Histone Deacetylases (HDACs) restores the positive charge on the lysine residues, leading to tighter binding between DNA and histones and repression of transcription. Histone Methylation: Histone methylation is another PTM that regulates gene expression. Unlike acetylation, methylation does not alter the charge of the lysine or arginine residues but instead adds a methyl group to the lysine or arginine residue. Methylation can occur on different lysine and arginine residues, and the extent of methylation can vary from mono- to tri-methylation. Depending on the location and extent of methylation, it can either promote or repress transcription. For example, methylation of lysine 4 on histone H3 (H3K4me3) is associated with active transcription, while methylation of lysine 9 and 27 on histone H3 (H3K9me and H3K27me) is associated with transcriptional repression. Histone Phosphorylation: Histone phosphorylation is a reversible PTM that regulates chromatin structure and function. Phosphorylation of histone H2A.X, a variant of histone H2A, is a critical event in the response to DNA damage, resulting in the recruitment of DNA repair factors to the site of damage. Phosphorylation of histone H3 at serine 10 (H3S10ph) and serine 28 (H3S28ph) is associated with transcriptional activation, while phosphorylation of histone H2B at serine 14 (H2BS14ph) is associated with transcriptional elongation. Histone Ubiquitination: Histone ubiquitination is a PTM that regulates nucleosome stability and chromatin remodeling. Ubiquitination of histone H2B at lysine 120 (H2BK120ub) is associated with transcriptional elongation and is required for the recruitment of the Polymerase-Associated Factor Complex (PAFc) to chromatin. Ubiquitination of histone H2A at lysine 119 (H2AK119ub) is associated with transcriptional repression and is required for the recruitment of the polycomb repressive complex (PRC) to chromatin. Histone SUMOylation: Histone sumoylation is a reversible process that involves the covalent attachment of SUMO to specific lysine residues on target proteins. In humans, there are four SUMO isoforms (SUMO-1, -2, -3, and -4), and the majority of histone SUMOylation occurs on histones H2A and H2B. Histone SUMOylation occurs on lysine residues located on the Nterminal tails of histones, which are unstructured and protrude from the nucleosome core particle. SUMOylation of histones is mediated by a cascade of enzymes that includes an E1 activating enzyme, an E2 conjugating enzyme, and E3 ligases that catalyze the transfer of SUMO from the E2 enzyme to the target lysine residue.

Conclusion

In conclusion, Post-Translational Modifications (PTMs) of histones play a crucial role in regulating gene expression and chromatin structure. The addition or removal of chemical groups to histone tails can alter the electrostatic interactions between histones and DNA, thereby affecting the accessibility of the chromatin to transcription factors and other regulatory proteins. Each of these modifications has a unique effect on histone function and can influence cellular processes such as DNA replication, repair, and transcription. In addition, PTMs of histones can be reversible or irreversible, and their regulation is tightly controlled by various enzymes and cofactors.