Epigenetic regulation plays an essential role in driving precise transcriptional programs during development and homeostasis. Among epigenetic mechanisms, histone mono-ubiquitination has emerged as an important post-transcriptional modification. Two major histone mono-ubiquitination events are the mono-ubiquitination of histone H2A at lysine 119 (H2AK119ub), placed by Polycomb repressive complex 1 (PRC1), and histone H2B lysine 120 mono-ubiquitination (H2BK120ub), placed by the heteromeric RNF20/RNF40 complex. Both of these events play fundamental roles in shaping the chromatin epigenetic landscape and cellular identity. In this review we summarize the current understandings of molecular concepts behind histone mono-ubiquitination, focusing on their recently identified roles in tissue development and pathologies.
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