Name: Harshin T

Course: 2nd Year 3rd Semester

Department: Department of Biotechnology

Reg no: 21L00331

COVALENT HISTONE MODIFICATIONS

Covalent Histone Modification is related to the primary changes that happen at the time of replication and
transcription. These changes are intervened by chromatin alteration modification, which are multiprotein buildings
that adjust histones post-translationally. The histone proteins are all altered synthetically. The N-terminal tails of the
histones are exposed to a great many post-translational covalent changes.
These modifications include Acetylation, histone tails undergoing methylation, Sumoylation,
Ubiquitylation, ADP ribosylation, Glycosylation, and Biotinylating. Most of these changes happen in
the tail regions, however, there are periodic modifications inside the histone fold( methylation of lysine
at the 79th place of histone H3).

The most common types of post-translational chemical modifications of histone are :

Acetylation :
Acetylation is a reaction that adds an acetyl functional group (acetoxy group, CH3CO) into an organic
chemical compound; to be specific the replacement of the acetyl group for a hydrogen atom, while
deacetylation is the elimination of an acetyl group from an organic chemical compound.. At the point
when a histone is acetylated, an acetyl group is added to at least one of its lysine deposits at the epsilon
amino group, by eliminating the positive charge. It reduces the affinity of the histone for DNA and
perhaps at the same time decreases the interaction between the individual nucleosome which prompts
the formation of the 30nm chromatin fiber.
Methylation :
Histone methylation is a process by which methyl groups are transferred to amino acids of histone
proteins that make up nucleosomes. Histone methylation is catalyzed by histone
methyltransferases(HMTs). The significant methylation locales inside histone tails are the fundamental
amino acid side chains of lysine and arginine residues. All referred to HMTs use S-adenosyl-
methionine as the methyl group donor.
Phosphorylation :
Phosphorylation happens in serine, threonine, and tyrosine present in the N-terminal histone tails. The
degrees of change are constrained by kinases and phosphatases which can add and eliminate the
phosphate group. All of the recognized histones move the hydroxyl group to phosphate(kinases) or
eliminate it from it(phosphatases) which influences downstream processes. Similarly, phosphorylation
of histone likewise fills in as an enrolling point for DNA damage and repair proteins.
ADP ribosylation :
The addition of ADP ribose can be distinguished in all four core histones as well as linked histone H1. These
changes are known to even out up to an increase in DNA damage implicating DNA damage response.

Ubiquitylation :
It involves the ubiquitination of histone with a 76 amino acid polypeptide which is joined to histone lysine.
ubiquitin is a small protein found in practically all tissues of eukaryotes.

Sumoylation :
The addition of SUMO protein (Small Ubiquitin-related Modifier) is a polypeptide of 97 amino acid residues
added to the carboxyl group and amino group that targets lysine in an objective protein. Sumoylation has been
recognized on all of the four core histones and functions by antagonizing acetylation and ubiquitylation.

References
● https://www.ncbi.nlm.nih.gov/pmc/articles/PMC86277/#:~:text=Acetylation%20of%20histone
%20N%2Dterminal,but%20also%20the%20nucleosome%20structure.
● https://rbej.biomedcentral.com/articles/10.1186/s12958-020-00637-5#:~:text=Histone
%20acetylation%20is%20a%20critical,cell%20cycle%20progression%20and
%20differentiation.
● https://thebiologynotes.com/covalent-histone-modification/
● https://www.nature.com/articles/nrc2876#:~:text=Modulation%20of%20chromatin%20through
%20covalent,replication%20and%20DNA%20damage%20repair.
● https://avacta.com/2014-06-25/#:~:text=Ubiquitylation%2C%20also%20referred%20to
%20as,organisms%2C%20to%20another%20targeted%20protein.