Reactome | SWI/SNF chromatin remodelers

SWI/SNF chromatin remodelers

Stable Identifier

R-HSA-9932451

Type

Pathway

Species

Homo sapiens

ReviewStatus

5/5

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Mammalian SWI/SNF complexes are ATP-dependent chromatin remodellers with a central catalytic ATPase consisting of either SMARCA2 (also known as BRM) or SMARCA4 (BRG1), bromodomain-containing proteins that bind acetylated histones (Hassan et al, 2002; Hyun et al, 2024; reviewed in Eustermann et al, 2024). In addition to SMARCA2/4, SWI/SNF complexes also contain varied organizations of 10-14 other proteins, many of which were initially identified as BAFs (BRM/BRG1 associated factors). This module describes the assembly of three well characterized SWI/SNF complexes, the canonical BAF (cBAF), equivalent to the SWI/SNF complex from S. cerevisiae, the polybromo-containing BAF (pBAF) (equivalent to the RSC complex from S. cerevisiae) and the more recently elucidated non-canonical BAF (ncBAF) (He et al, 2020; Mashtalir et al, 2018; Mashtalir et al, 2020; Wang et al, 2022; Yuan et al, 2022; Alpsoy and Dykhuizen, 2018; Michel et al, 2018). All three complexes share catalytic subunits (SMARCA2 or SMARCA4) as well as combinations of 5 other common proteins/protein families (ACTB, ACTL6A/B, BCL7A/B/C, SMARCD1/2/3 and SMARCC1/2) and are additionally distinguished by complex-specific subunits (He et al, 2020; Mashtalir et al, 2018; Wang et al, 2022; Yuan et al, 2022; Alpsoy and Dykhuizen, 2018; Eustermann et al, 2024). In addition to these three complexes, other SWI/SNF complexes have been identified that play tissue-, cell- or developmental-specific roles (see for instance, Lessard et al, 2007; Ho,Ronan et al, 2009; Ho, Jothi et al, 2009; Zhang et al, 2014) but fundamentally all are involved in chromatin assembly or remodelling through alterations of histone-DNA contacts (reviewed in Eustermann et al, 2024; Cenik and Shilatifard, 2021). Mutations in components of SWI/SNF complexes are frequent in cancers and other diseases (Kadoch et al, 2013; reviewed in Mittal and Roberts, 2020; Kadoch and Crabtree, 2015; Cenik and Shilatifard, 2021; Wang and Tang, 2023).
Cryo-EM, cross-linking and gradient sedimentation have revealed the modular organization of mammalian SWI/SNF complexes (He et al, 2020; Mashtalir et al, 2018; Mashtalir et al, 2020). The ATPase module contains most of the catalytic portion of the SMARCA2/4 protein and wraps around the nucleosomal DNA. Closely associated with the catalytic module is a domain consisting of ACTB and ACTL6A/B, as well as SMARCB1 and BCL7 paralogs. A core or base module consisting of the SMARCC dimer and SMARCE1, supplemented by many of the complex-specific subunits, makes contact with the bottom side of the nucleosome (He et al, 2020).

Literature References

PubMed ID	Title	Journal	Year
30343899	Modular Organization and Assembly of SWI/SNF Family Chromatin Remodeling Complexes 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	Cell	2018
19279220	An embryonic stem cell chromatin remodeling complex, esBAF, is essential for embryonic stem cell self-renewal and pluripotency Ho, L, Ronan, JL, Wu, J, Staahl, BT, Chen, L, Kuo, A, Lessard, J, Nesvizhskii, AI, Ranish, J, Crabtree, GR	Proc Natl Acad Sci U S A	2009
12419247	Function and selectivity of bromodomains in anchoring chromatin-modifying complexes to promoter nucleosomes Hassan, AH, Prochasson, P, Neely, KE, Galasinski, SC, Chandy, M, Carrozza, MJ, Workman, JL	Cell	2002
36496390	Structure of nucleosome-bound human PBAF complex Wang, L, Yu, J, Yu, Z, Wang, Q, Li, W, Ren, Y, Chen, Z, He, S, Xu, Y	Nat Commun	2022
17640523	An essential switch in subunit composition of a chromatin remodeling complex during neural development Lessard, J, Wu, JI, Ranish, JA, Wan, M, Winslow, MM, Staahl, BT, Wu, H, Aebersold, R, Graef, IA, Crabtree, GR	Neuron	2007
39511190	The BAF complex enhances transcription through interaction with H3K56ac in the histone globular domain Hyun, K, Ahn, J, Kim, H, Kim, J, Kim, YI, Park, HS, Roeder, RG, Lee, JE, Kim, J	Nat Commun	2024
23644491	Proteomic and bioinformatic analysis of mammalian SWI/SNF complexes identifies extensive roles in human malignancy Kadoch, C, Hargreaves, DC, Hodges, C, Elias, L, Ho, L, Ranish, J, Crabtree, GR	Nat Genet	2013
30397315	A non-canonical SWI/SNF complex is a synthetic lethal target in cancers driven by BAF complex perturbation Michel, BC, D'Avino, AR, Cassel, SH, Mashtalir, N, McKenzie, ZM, McBride, MJ, Valencia, AM, Zhou, Q, Bocker, M, Soares, LMM, Pan, J, Remillard, DI, Lareau, CA, Zullow, HJ, Fortoul, N, Gray, NS, Bradner, JE, Chan, HM, Kadoch, C	Nat Cell Biol	2018
26601204	Mammalian SWI/SNF chromatin remodeling complexes and cancer: Mechanistic insights gained from human genomics Kadoch, C, Crabtree, GR	Sci Adv	2015
35477757	Structure of human chromatin-remodelling PBAF complex bound to a nucleosome Yuan, J, Chen, K, Zhang, W, Chen, Z	Nature	2022
19279218	An embryonic stem cell chromatin remodeling complex, esBAF, is an essential component of the core pluripotency transcriptional network Ho, L, Jothi, R, Ronan, JL, Cui, K, Zhao, K, Crabtree, GR	Proc Natl Acad Sci U S A	2009
32958894	COMPASS and SWI/SNF complexes in development and disease Cenik, BK, Shilatifard, A	Nat Rev Genet	2021
38081975	Energy-driven genome regulation by ATP-dependent chromatin remodellers Eustermann, S, Patel, AB, Hopfner, KP, He, Y, Korber, P	Nat Rev Mol Cell Biol	2024
32001526	Structure of nucleosome-bound human BAF complex He, S, Wu, Z, Tian, Y, Yu, Z, Yu, J, Wang, X, Li, J, Liu, B, Xu, Y	Science	2020
33053319	A Structural Model of the Endogenous Human BAF Complex Informs Disease Mechanisms Mashtalir, N, Suzuki, H, Farrell, DP, Sankar, A, Luo, J, Filipovski, M, D'Avino, AR, St Pierre, R, Valencia, AM, Onikubo, T, Roeder, RG, Han, Y, He, Y, Ranish, JA, Dimaio, F, Walz, T, Kadoch, C	Cell	2020
32303701	The SWI/SNF complex in cancer - biology, biomarkers and therapy Mittal, P, Roberts, CWM	Nat Rev Clin Oncol	2020
25241744	Transcriptional repression by the BRG1-SWI/SNF complex affects the pluripotency of human embryonic stem cells Zhang, X, Li, B, Li, W, Ma, L, Zheng, D, Li, L, Yang, W, Chu, M, Chen, W, Mailman, RB, Zhu, J, Fan, G, Archer, TK, Wang, Y	Stem Cell Reports	2014
29374058	Glioma tumor suppressor candidate region gene 1 (GLTSCR1) and its paralog GLTSCR1-like form SWI/SNF chromatin remodeling subcomplexes Alpsoy, A, Dykhuizen, EC	J Biol Chem	2018
37031881	SWI/SNF complexes and cancers Wang, L, Tang, J	Gene	2023