This document discusses histone modifications through acetylation and methylation. It explains that DNA wraps around histone proteins to form nucleosomes. Histone tails can be modified through acetylation and methylation, which are regulated by specific enzyme complexes. These modifications affect chromatin structure and transcription by altering the interaction of histone tails with DNA and recruiting other proteins. The combination of modifications on histone tails is referred to as the "histone code", which is read by protein complexes to influence gene expression.

1. Histone Modifications:
Acetylation and Methylation
Somanna A. N.

2. • Complexes of DNA and protein form
Eukaryotic chromosmes.
• These proteins are divided into two classes:
Histones and nonhistone chromosomal
proteins.
• Histones are responsible for most basic level of
chromosome packing – Nucleosome, a
protein-DNA complex.

4. Nucleosome
• DNA wound around a histone core
• Made of ‘nucleosome core particle’ and ‘linker DNA’

5. Histone Core
• An octamer of 4 histone proteins- H2A, H2B, H3 and
H4.
• Each histone protein has a structured domain,
‘Histone Fold’ and unstructured ‘N- terminal tail’.

6. • Histone tails are involved in the 30-nm fibre formation by
forming H bonds with adjacent nucleosome tails.
• Histone tails provide site for covalent modifications-
Acetylation, Methylation, Phosphorylation, etc.
• Such modifications determine the interaction of histone with
other proteins, which may in turn regulate chromatin
structure, and transcription, etc.

7. • Modifications of N- terminal tails reduce ability of
nucleosome arrays to form repressive structures and
creating sites that can recruit other proteins.
• It has been proposed that these modifications result
in a ‘code’ which can be read by proteins involved in
gene expression and other DNA transcations.

8. Acetylation
• It is the introduction of an Acetyl functional group to the
Lysine amino acid of the histone tail.
• These reactions are catalyzed by enzymes with "histone
acetyltransferase" (HAT) or "histone deacetylase" (HDAC)
activity.

9. • Acetylation removes +ve charge of the histone tail,
reducing affinity for the –ve charged phosphate
groups of DNA
• It also reduces affinity of tail for adjacent
nucleosomes, thus affecting ability of nucleosome
arrays to form more repressive higher-ordered
chromatin structures.
• Also, acetylation is involved in nucleosome assembly
and interaction of histone with other regulatory
proteins, creating a transcription permissive
environment.

10. • Modification of histone tails by acetylation is known to
increase the access of transcription factors to DNA through
structural changes in nucleosomes or nucleosomal arrays.
Acetylated histones are also specifically recognized by other
proteins. The bromodomain, found in transcription factors
and HATs allows for the preferential recognition of histone
tails when they are acetylated at specific lysine residues

11. Methylation
• It is the introduction of an Methyl functional group to Lysine
or Arginine of the histone tail.
• These reactions are catalyzed by enzymes with "histone
methyltransferase”
• ‘Arg’ can be methylated once or twice, and ‘Lys’ once, twice of
trice.

12. • Methylation does not neutralize charge but recruit
silencing or regulatory proteins that bind methylated
histones.
• Chromodomain containing proteins interact with
methylated histone tails.

13. • Methylation generally associated with transcription
repression, but specific methylations result in
activation.
• They can loosen the tail allowing transcription factors
to access DNA or encompass the tails around DNA
restricting access

14. Histone Code
• The histone tail modifications can occur in varoius
combinations, many of which have specific meaning- HISTONE
CODE.
• This code is read by specific protein complexes which contain
protein modules which recognise specefic histone marks and
bind to them.