Histone modifications
- 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.