Histone Lysine ubiquitination

Ubiquitination (ub) is a bulky modification to the small histone peptides. Each ubiquitin group adds approx 8.5 kDa and there are multiple such moieties attached to single lysine in case of polyubiquitination. Ubiquitination generally targets proteins for proteasomal degradation but in case of histones it provides other signals important for gene regulation. Ubiquitination is catalysed by a group of ligases named 'Lysine ubiquitinases'.

Ubiquitination is achieved by ligation of C-terminus of ubiquitin to the e-amino group of the lysine residues. It can be of multiple types like mono, di or polyubiquitination. Polyubiquitination is achieved by crosslinking several ubiquitin moieties to each other to form:

Linear chains: C-terminus of each ubiquitin bonds with free N-terminus of the preceding ubiquitin.

Branched chains: C-terminus of each ubiquitin links to e-amino group present on lysine at 63 position of another ubiquitin forming a polymer. It is also referred to as 'K63-linked polyubiquitination'.

Mixed chains: Linear chains with random branches.

Such 'Lysine-63' linked polyubiquitylation on Histone H2A and gamma-H2A.X by RNF8 and RNF168 are known to protect genome integrity by licensing the DSB-flanking chromatin to concentrate repair factors near the DNA lesions. Monoubiquitination is often associated with transcriptional repression.


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Sites of histone Lysine ubiquitination
Site of modification Writers Erasers
H2AK119ub E3 ubiquitin-protein ligase RING2, E3 ubiquitin-protein ligase RING1 Histone H2A deubiquitinase MYSM1
H2AK121ub E3 ubiquitin-protein ligase RING2
H2BK120ub E3 ubiquitin-protein ligase BRE1A, E3 ubiquitin-protein ligase RBX1, E3 ubiquitin-protein ligase BRE1B
H4K91ub E3 ubiquitin-protein ligase DTX3L