For a healthy histone code, a little SUMO in the tail keeps the acetyl away

Abstract

Chemical modification of histones through a growing number of post-translational mechanisms is an integral part of transcription. A recent report provides exciting new evidence that conjugation of the ubiquitin-like protein SUMO to histones opposes acetylation and establishes SUMOylation as an important histone mark linked to transcriptional repression.

Figure 1. SUMOylation pathway

1) Initial processing of SUMO precursor by SUMO specific proteases (SENP) removes C terminal residues to generate a new GlyGly C terminus. 2) ATP dependent activation of SUMO by the SUMO specific E1 leads to the formation of a thioester bond between the C terminus of SUMO and a cysteine in the SAE2 subunit. 3) The SUMO moiety is transferred to the SUMO E2 ligase UBC9 through a trans-esterification reaction. 4) Ubc9 catalyzed conjugation of SUMO to substrate leads to the formation of an isopeptide bond between the C terminus of SUMO and the amino group of the target lysine. This step is enhanced by E3 ligases. 5) SUMO conjugation is reversible through the isopeptidase activity of SUMO-specific proteases.

Figure 2. SUMOylation antagonizes acetylation

Model of a nucleosome core showing a single surface rendered SUMO molecule conjugated to K6 of one of the H2B N terminal tails. The basic surface in SUMO essential for its transcriptional repressive function is circled.