Laura D. Gallego Valle, MSc
MedUni Wien RESEARCHER OF THE MONTH, November 2017
Histone ubiquitination in detail – a molecular snapshot
There are about 20.000 protein-coding genes in humans, however, only a small number are activated in any given cell. To manage genetic information, nature has evolved a sophisticated system that facilitates access to specific genes relying on a DNA-histone protein complex called the nucleosome. Postranslational modifications of the histones enables additional levels of gene expression control. Several human diseases are linked to the mutation or loss of histone modifications, making it important to understand their regulation. One of these modifications is ubiquitination, which consist on the attachment of a small protein called ubiquitin to lysine residues on the histones.
Histone H2B ubiquitination on Lysine 123 (Lysine 120 in humans) is mediated by the E3 ligase Bre1 (human RNF20/40) and the E2 conjugating enzyme Rad6. In the recent publication, cross-linking couple to mass spectrometry analyses permitted to capture the transient interactions mediating this ubiquitination event. These results allowed elucidating the exact molecular mechanism of how the Bre1/Rad6 complex recognizes the nucleosomal surface, how the high specificity towards the Lysine 123 on histone H2B is achieved and how they might compete with other nuclear factors for its regulation during transcription. These findings provide a detailed mechanism for a specific ubiquitination modification with several implications in the cell.
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