Autor: |
Yi Zhang, Guojia Xie, Ji-Eun Lee, Mohamad Zandian, Deepthi Sudarshan, Benjamin Estavoyer, Caroline Benz, Tiina Viita, Golareh Asgaritarghi, Catherine Lachance, Clémence Messmer, Leandro Simonetti, Vikrant Kumar Sinha, Jean-Philippe Lambert, Yu-Wen Chen, Shu-Ping Wang, Ylva Ivarsson, El Bachir Affar, Jacques Côté, Kai Ge, Tatiana G. Kutateladze |
Jazyk: |
angličtina |
Rok vydání: |
2024 |
Předmět: |
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Zdroj: |
Nature Communications, Vol 15, Iss 1, Pp 1-15 (2024) |
Druh dokumentu: |
article |
ISSN: |
2041-1723 |
DOI: |
10.1038/s41467-024-49391-x |
Popis: |
Abstract The human methyltransferase and transcriptional coactivator MLL4 and its paralog MLL3 are frequently mutated in cancer. MLL4 and MLL3 monomethylate histone H3K4 and contain a set of uncharacterized PHD fingers. Here, we report a novel function of the PHD2 and PHD3 (PHD2/3) fingers of MLL4 and MLL3 that bind to ASXL2, a component of the Polycomb repressive H2AK119 deubiquitinase (PR-DUB) complex. The structure of MLL4 PHD2/3 in complex with the MLL-binding helix (MBH) of ASXL2 and mutational analyses reveal the molecular mechanism which is conserved in homologous ASXL1 and ASXL3. The native interaction of the Trithorax MLL3/4 complexes with the PR-DUB complex in vivo depends solely on MBH of ASXL1/2, coupling the two histone modifying activities. ChIP-seq analysis in embryonic stem cells demonstrates that MBH of ASXL1/2 is required for the deubiquitinase BAP1 recruitment to MLL4-bound active enhancers. Our findings suggest an ASXL1/2-dependent functional link between the MLL3/4 and PR-DUB complexes. |
Databáze: |
Directory of Open Access Journals |
Externí odkaz: |
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