Histone modifications like methylation, phosphorylation, and acetylation are important epigenetic mechanisms that regulate gene expression. Histone methylation can result in activation or repression and involves histone lysine and arginine methyltransferases. Histone phosphorylation occurs on specific serine and threonine residues by histone kinases. Histone acetylation is mediated by histone acetyltransferases and deacetylases and favors transcriptional activation by reducing the interaction between histones and DNA.

1. Histone Modifications
Ajay Prakash Uniyal
M.Sc Life Sciences
Central University Of Punjab
Reffered Prof Ranganrajan, Niiptel, IISC Banglore Slide

3. Histone Methylation
Histone methylation can result in both activation and repression.
Employs Two enzyme HKMTs (Histone Lysine Methyl Transferase) and HRMT (Histone Arginine
Methyl Transferases)
First HKMT, SUV39H1 methylates Lysine 9 of H3. SET domain conserved core of histone
methyltransferases.
H4KMe--Set1p
H9KMe- SUV39H1.
H3K9 correlates with heterochromatin formation.
Methylation of H3-K4 specially impairs methylation of H3 K9 blocking heterochromatin
formation.

4. • Dimethyl H3K4 is assosciated with euchromatic region.
• Initiation and maintenance of heterochromatin is by H3k9.
• Mammalian HMTs which methylate lysine 4 of Histone H3 are : SET1, SET7 and SMYD3.
• H3K27 is assosciated with transcriptional repression.
• H3K27 methylation is catalysed by multi-molecular complex referred to as polycomb
repressive complexes (PRC).
• Methylated lysines are recognised by Chromodomains.

5. • Example of Chromodomain containing proteins
1. HP1
2. Drosophilia Polycomb Protein.
• HP1 and PC recognise H3K9 and K3K27.
• Catalytic Domain that methyaltes Arginine is known as PRMT.
• PRMT domain transfers the methyl group from s adenosyl methionine to guanido group of
arginine to produce monomethylarginine and dimethylarginine.
• Methylation of arginine 3 of histone H4 facialtes H4 and activates transcription activation by
nuclear hormone receptor.
• Histone Methyaltion was thought to be extremely stable modifications.

6. Histone Phosphorylation
Specific serine and threonine residues are phosphorylated by Histone Kinase.
H2A : S1
H2B : S14
H3 : S3
H4 : S1
Phosphorylation of Histone H3 at T45 occurs after activation of DNA damage signalling
pathways and are mediated by protein kinase c.
Histone H4 is phosphorylated not only on serine 1 but also on histidines 18 and 75.

7. HISTONE ACETYLATION
• Histone acetyaltion are essential for gene regulation.
• Employs enzyme HAT , reversed by HDAC.
• Acetyl group is transferred from acetyl coa to lysine n terminal tail.
• Acetylation removes the positive charge thus decrease the interaction of N termini
of histone with negatively charged phosphate groups.
• Transcriptionally active DNA is called euchromatin. Condensed packed DNA is called
heterochromatin.
• Histone acetylation favours
euchromatic region i.e. it favours
transcriptional activation.