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

被引：502

作者：

Mashtalir, Nazar ^{[1
,2
,3
]}

D'Avino, Andrew R. ^{[1
,2
,3
]}

Michel, Brittany C. ^{[1
,2
,3
,4
]}

Luo, Jie ^{[5
]}

Pan, Joshua ^{[1
,2
,3
,4
]}

Otto, Jordan E. ^{[1
,2
,3
,6
]}

Zullow, Hayley J. ^{[1
,2
,3
,4
]}

McKenzie, Zachary M. ^{[1
,2
]}

Kubiak, Rachel L. ^{[1
,2
]}

Pierre, Roodolph St. ^{[1
,2
,3
,6
]}

Valencia, Alfredo M. ^{[1
,2
,3
,6
]}

Poynter, Steven J. ^{[1
,2
,3
,6
]}

Cassel, Seth H. ^{[1
,2
,3
,4
]}

Ranish, Jeffrey A. ^{[5
]}

Kadoch, Cigall ^{[1
,2
,3
]}

机构：

[1] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02215 USA

[2] Harvard Med Sch, Boston, MA 02215 USA

[3] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA

[4] Harvard Med Sch, Biol & Biomed Sci Grad Program, Boston, MA 02215 USA

[5] Inst Syst Biol, Seattle, WA 98109 USA

[6] Harvard Univ, Chem Biol Program, Cambridge, MA 02138 USA

来源：

CELL | 2018年 / 175卷 / 05期

关键词：

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

D O I：

10.1016/j.cell.2018.09.032

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：1272 / +

页数：37

共 43 条

[1] Glioma tumor suppressor candidate region gene 1 (GLTSCR1) and its paralog GLTSCR1-like form SWI/SNF chromatin remodeling subcomplexes [J].