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BAP1 complex promotes transcription by opposing PRC1-mediated H2A ubiquitylation
Antoine Campagne1,2, Ming-Kang Lee1,2, Dina Zielinski1,2,3
1Institut Curie, Paris Sciences et Lettres Research University, Sorbonne University, 75005, Paris, France.
Nature Communications
|January 22, 2019
Summary
The BAP1 protein complex (BAP1.com) unexpectedly activates gene expression, not silencing. It protects active genes from Polycomb Repressive Complex 1, revealing a new role for BAP1 in transcriptional regulation.
Area of Science:
- Molecular Biology
- Epigenetics
- Cancer Biology
Background:
- The Calypso-ASX complex in Drosophila deubiquitinates H2A and functions in Polycomb-mediated transcriptional silencing.
- Mammalian homologs BAP1 and ASXL1/2/3 are frequently mutated in cancers, but their roles are not fully understood.
Purpose of the Study:
- To elucidate the precise functions of the mammalian BAP1 and ASXL proteins.
- To investigate the role of BAP1 in transcriptional regulation and its association with the Polycomb machinery.
Main Methods:
- Utilized CRISPR/Cas9 technology to generate isogenic cell lines.
- Employed an integrative approach to study BAP1 complex formation and function.
- Investigated the mechanism of BAP1.com-mediated transcriptional regulation.
Main Results:
- Discovered a novel role for BAP1 in gene activation, distinct from Polycomb-mediated silencing.
- Demonstrated that BAP1 function requires an enzymatically active BAP1-associated core complex (BAP1.com) with ASXL proteins.
- Showed that BAP1.com safeguards transcriptionally active genes against Polycomb Repressive Complex 1 (PRC1) silencing.
Conclusions:
- BAP1, as part of the BAP1.com complex, functions in gene activation rather than silencing.
- BAP1.com acts as a crucial regulator by protecting active genes from repression by PRC1.
- These findings reveal a new paradigm for BAP1 function in transcriptional control and cancer biology.
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