Title | Modular Organization and Assembly of SWI/SNF Family Chromatin Remodeling Complexes. |
Publication Type | Journal Article |
Year of Publication | 2018 |
Authors | Mashtalir N, D'Avino AR, Michel BC, Luo J, Pan J, Otto JE, Zullow HJ, McKenzie ZM, Kubiak RL, St Pierre R, Valencia AM, Poynter SJ, Cassel SH, Ranish JA, Kadoch C |
Journal | Cell |
Volume | 175 |
Issue | 5 |
Pagination | 1272-1288.e20 |
Date Published | 2018 11 15 |
ISSN | 1097-4172 |
Keywords | Animals, Chromatin, Chromatin Assembly and Disassembly, Chromosomal Proteins, Non-Histone, Drosophila, Gene Knockout Techniques, HEK293 Cells, Humans, Mass Spectrometry, Mutagenesis, Protein Subunits, Recombinant Proteins, Transcription Factors |
Abstract | 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 cancer and developmental disorders. To date, the modular organization and pathways 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 evolutionarily 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. |
DOI | 10.1016/j.cell.2018.09.032 |
Alternate Journal | Cell |
PubMed ID | 30343899 |
PubMed Central ID | PMC6791824 |
Grant List | DP2 CA195762 / CA / NCI NIH HHS / United States P50 GM076547 / GM / NIGMS NIH HHS / United States R01 GM110064 / GM / NIGMS NIH HHS / United States |
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