Abstract
Histones are main components of chromatin, and the protein levels of histones significantly affect chromatin assembly. However, how histone protein levels are regulated, especially whether and how histones are degraded, is largely unclear. Here, we found that histone H2B is mainly degraded through the proteasome-mediated pathway, and the lysine-120 site of H2B is essential for its K48-linked polyubiquitination and degradation. Moreover, the degradation-impaired H2BK120R mutant shows an increased nucleolus localization, and inhibition of the proteasome results in an elevated nucleolus distribution of wild-type H2B, which is similar to that of H2BK120R mutants. More importantly, the nucleolus fractions can ubiquitinate and degrade the purified H2B in vitro, suggesting that the nucleolus, in addition to its canonical roles regulating ribosome genesis and protein translation, likely associates with H2B degradation. Therefore, these findings revealed a novel mechanism for the regulation of H2B degradation in which a nucleolus-associated proteasome pathway is involved.