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WAC, a functional partner of RNF20/40, regulates histone H2B ubiquitination and gene transcription.

Zhang F., Yu X.

Histone H2B ubiquitination plays an important role in regulating chromatin organization during gene transcription. It has been shown that RNF20/40 regulates H2B ubiquitination. Here, using protein affinity purification, we have identified WAC as a functional partner of RNF20/40. Depletion of WAC abolishes H2B ubiquitination. WAC interacts with RNF20/40 through its C-terminal coiled-coil region and promotes RNF20/40 s E3 ligase activity for H2B ubiquitination. The N-terminal WW domain of WAC recognizes RNA polymerase II. During gene transcription, WAC targets RNF20/40 to associate with RNA polymerase II complex for H2B ubiquitination at active transcription sites, which regulates transcription. Moreover, WAC-dependent transcription is important for cell-cycle checkpoint activation in response to genotoxic stress. Taken together, our results demonstrate an important regulator for transcription-coupled histone H2B ubiquitination.

Mol. Cell 41:384-397(2011) [PubMed] [Europe PMC]

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