Modular Organization and Assembly of SWI/SNF Family Chromatin Remodeling Complexes

作者：Mashtalir, Nazar; D'Avino, Andrew R.; Michel, Brittany C.; Luo, Jie; Pan, Joshua; Otto, Jordan E.; Zullow, Hayley J.; McKenzie, Zachary M.; Kubiak, Rachel L.; Pierre, Roodolph St.; Valencia, Alfredo M.; Poynter, Steven J.; Cassel, Seth H.; Ranish, Jeffrey A.; Kadoch, Cigall^*

来源：Cell, 2018, 175(5): 1272-+.

DOI：10.1016/j.cell.2018.09.032

• BAF COMPLEX
• TRANSCRIPTION
• SWI2/SNF2
• PROTEINS
• ROLES

Mammalian SWI/SNF (mSWI/SNF) ATP-dependent chromatin remodeling complexes are multi-subunit molecular machines that play vital roles in regulating genomic architecture and are frequently disrupted in human ca; and developmental disorders. To date, the modular organization and path- ways of assembly of these chromatin regulators remain unknown, presenting a major barrier to structural and functional determination. Here, we elucidate the architecture and assembly pathway across three classes of mSWI/SNF complexes-canonical BRG1/BRM-associated factor (BAF), polybromo-associated BAF (PBAF), and newly defined ncBAF complexes-and define the requirement of each subunit for complex formation and stability. Using affinity purification of endogenous complexes from mammalian and Drosophila cells coupled with cross-linking mass spectrometry (CX-MS) and mutagenesis, we uncover three distinct and evolutionailry conserved modules, their organization, and the temporal incorporation of these modules into each complete mSWI/SNF complex class. Finally, we map human disease-associated mutations within subunits and modules, defining specific topological regions that are affected upon subunit perturbation.

• 出版日期2018-11-15