snapshot: chromatin remodeling:swi/snf...snapshot: chromatin remodeling: swi/snf margaret m. kasten,...

See online version for legend and references310 Cell 144, January 21, 2011 ©2011 Elsevier Inc. DOI 10.1016/j.cell.2011.01.007

SnapShot: Chromatin Remodeling: SWI/SNFMargaret M. Kasten, Cedric R. Clapier, and Bradley R. CairnsHHMI, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USA

Arp7

Arp9Swi2/Snf2Swp73

Swi3Swi3

Swi3

Swi1/Adr6

Swi3

Swi3Swi3Swi3Swi3

Swi1/

Swi3

Swi1/Adr6Adr6

Swi3Swi3Swi3

Swi1/Adr6Adr6

Snf5

Swi3Swi3Swi3

Swi3Swi3Swi3Swi3Swi3Swi3Swi3Swi3Swi3Swi3Swi3Swi3

Swp82 Snf6

Snf11

BAP111/dalao

BAP55

Actin

BAP111/BAP111/

BAP55BAP55BAP55

ActinActin

BAP111/dalaodalao

BAP55BAP55

ActinActinBrahma

BAF170

ActinActinActinActinActinActin

BAF170BAF170

Polybromo

Osa/EyelidBAP

PBAP

BAF57 BAF53a,b

β-actin

BAF200BAF200BAF200

BAF180

Snf5

Swp73Swp73Swp73Swp73Swp73Swp73Swp73Swp73Swp73Swp73Swp73Swp73Swp73Swp73Swp73Swp73Swp73Swp73Swp73Swp73Swp73Swp73

Snf5

Swp73Swp73

Snf5

Swp73Swp73Swp73Swp73Swp73Swp73Swp73Swp73Swp73Swp73Swp73Swp73Swp73Swp73Swp73Swp73Swp73Swp73Swp73

BAF250a,b/hOSA1

BAF200BAF200BAF200BAF200

BAF180BAF180BAF180BAF180BAF180BAF180BAF180BAF180BAF180

BRD7

BAF

PBAF

Yeast SWI/SNF Yeast RSC

Fly BAP/PBAP Human BAF/PBAF

Pol II activationElongationDSB repairDNA replication

Pol II and Pol III activationDSB repairCell signalingCell-cycle progression, spindle-assembly checkpointChromosome/plasmid segregation, cohesion

Pol II regulationElongationCell-cycle/proliferationImmune system functionDevelopment (Metamorphosis)

ElongationDSB repair, nucleotide excision repairSignalingProliferation and differentiationStem cell self-renewal/pluripotencyDNA replicationSplicingTumor SuppressorDevelopment

Catalytic ATPase with bromodomain

Additionalbromodomainsubunits

Actin-like Subfamilyspecific

SUBUNIT LEGENDTranscription DNA repair Cell-cycle and Differentiation Others

Composition and functions of the SWI/SNF family of remodelers

Remodeler/nucleosome complex

Taf14Snf11Snf11Snf11Snf11Snf11Snf11

Fly BAP/PBAPFly BAP/PBAPFly BAP/PBAPFly BAP/PBAPFly BAP/PBAPFly BAP/PBAPFly BAP/PBAPFly BAP/PBAPFly BAP/PBAPFly BAP/PBAPFly BAP/PBAPFly BAP/PBAP

Snf11Snf11Snf11Snf11Snf11Snf11Snf11Snf11Snf11Snf11 Taf14Taf14Taf14Taf14Taf14Taf14Taf14Taf14

TEXT LEGEND

Taf14Taf14Taf14Taf14

Rtt102

Yeast SWI/SNFYeast SWI/SNFYeast SWI/SNFYeast SWI/SNFYeast SWI/SNFYeast SWI/SNFYeast SWI/SNFYeast SWI/SNFYeast SWI/SNFYeast SWI/SNFYeast SWI/SNFYeast SWI/SNFYeast SWI/SNFYeast SWI/SNFYeast SWI/SNFYeast SWI/SNFYeast SWI/SNFYeast SWI/SNFYeast SWI/SNFYeast SWI/SNF

Composition and functions of the SWI/SNF family of remodelersComposition and functions of the SWI/SNF family of remodelersComposition and functions of the SWI/SNF family of remodelersComposition and functions of the SWI/SNF family of remodelers

Snf6Snf6

Yeast SWI/SNFYeast SWI/SNFYeast SWI/SNFYeast SWI/SNFYeast SWI/SNFYeast SWI/SNFYeast SWI/SNFYeast SWI/SNF

Swi2/Snf2Swi2/Snf2Swi2/Snf2Swi2/Snf2Swi2/Snf2Swi2/Snf2Swi2/Snf2Swi2/Snf2Swi2/Snf2Swi2/Snf2Swi2/Snf2Swi2/Snf2Swi2/Snf2Swi2/Snf2

Snf6Snf6Snf6Snf6Snf6Snf6Snf6Snf6Snf6 Arp7Arp7Arp7Arp7Arp7Snf6Snf6Snf6Snf6Snf6 Arp7Arp7Arp7

Arp9Arp9Arp9Arp9Arp9Arp9Arp9

Rtt102Rtt102Rtt102Rtt102Rtt102Rtt102Rtt102Rtt102Rtt102Rtt102Rtt102Rtt102Rtt102Rtt102Rtt102Rtt102Rtt102Rtt102Rtt102Rtt102Rtt102Rtt102Rtt102Rtt102Rtt102Rtt102Rtt102Rtt102Rtt102Rtt102

Rsc5

Arp7

Arp9

Rtt102

Yeast RSC Yeast RSC Yeast RSC

Rsc7

Rsc3

Yeast RSC Yeast RSC Yeast RSC Yeast RSC Yeast RSC Yeast RSC Yeast RSC Yeast RSC

Rsc30

Rtt102Rtt102Rtt102

Rsc14/Ldb7

Rsc30Rsc30Rsc30Rsc30Rsc30Rsc30Rsc30

Htl1

Rsc30Rsc30Rsc30 Rsc3Rsc3Rsc3Rsc3Rsc3Rsc30Rsc30

Arp7Arp7Arp7Arp7Arp7Arp7Arp7Arp7Arp7Arp7Rsc14/Rsc14/Rsc14/Rsc14/

Rsc3Rsc3Rsc3Rsc14/Rsc14/Rsc14/Rsc14/Rsc14/Rsc14/Rsc14/Rsc14/Rsc14/Rsc14/Rsc14/Rsc14/Rsc14/Ldb7Ldb7

Rsc14/Rsc14/Rsc14/Rsc14/Rsc14/Rsc14/Rsc14/Rsc14/Rsc14/Rsc14/Rsc14/Rsc14/Rsc14/Rsc14/Ldb7Ldb7Ldb7Ldb7Ldb7Ldb7Ldb7Ldb7Ldb7Ldb7Ldb7Ldb7Ldb7Ldb7Ldb7Ldb7Ldb7Ldb7Ldb7Ldb7Ldb7Ldb7Ldb7Ldb7Ldb7Ldb7

Sth1

Rsc3Rsc3Rsc30Rsc30 Rsc3Rsc3Rsc3Rsc30 Rsc3Rsc3Rsc3Rsc3Rsc3Rsc3

Htl1Htl1Htl1Htl1

Rsc6

Rsc4

Yeast RSC Yeast RSC Yeast RSC Yeast RSC Yeast RSC Yeast RSC Yeast RSC Yeast RSC Yeast RSC

Rsc30Rsc30Rsc30Rsc30Rsc30Rsc30Rsc30

Rsc7Rsc7

spindle-assembly checkpoint

Rsc30Rsc30Rsc30Rsc30Rsc30Rsc30Rsc30Rsc30

Rsc7Rsc7Rsc7Rsc7Rsc7Rsc8/Swh3

Rsc7Rsc7Rsc7Rsc7Rsc7Rsc8/Swh3Swh3

Rsc8/Swh3

spindle-assembly checkpoint Rsc9

Ldb7Ldb7Ldb7Ldb7Ldb7Ldb7Ldb7Ldb7Ldb7Ldb7Ldb7Ldb7Ldb7Ldb7Ldb7Ldb7Ldb7Htl1Htl1Htl1Htl1 Ldb7Ldb7Rsc8/Swh3Swh3

Sfh1

Rtt102

Arp7Arp7Arp7Arp7Arp7

Rtt102Rtt102Rtt102Rtt102Rtt102Rtt102Rtt102Rtt102Rtt102Rtt102Rtt102Rtt102Rtt102Rtt102Rtt102

Rsc10/Rsc56

Rtt102

Rsc5Rsc5Rsc5

Arp9Arp9Arp9Arp9Arp9Arp9Arp9Arp9Arp9Arp9Arp9

Rtt102Rtt102Rtt102Rtt102Rtt102Rtt102Rtt102

Arp9Arp9

Rtt102Rtt102Rtt102Rtt102

Arp9Arp9Arp9Arp9Arp9Arp9Sth1Sth1Sth1Sth1Sth1Sth1

Sfh1 Rsc10/Rsc10/Rsc10/Rsc10/Rsc10/Rsc10/Rsc10/Rsc10/Rsc10/Rsc10/Rsc10/Rsc10/Rsc10/Rsc10/Rsc10/Rsc10/Rsc10/Rsc10/Rsc10/Rsc10/Rsc10/Rsc10/Rsc10/Rsc10/Rsc10/Rsc10/Rsc10/Rsc10/Rsc10/Rsc10/Rsc10/Rsc10/Rsc10/Rsc10/Rsc56Rsc56Rsc56Rsc56Rsc56Rsc56Rsc56Rsc56Rsc56Rsc56Rsc56Rsc56Rsc56Rsc56Rsc56Rsc56Rsc56Rsc56Rsc56Rsc56Rsc56Rsc56Rsc56Rsc56Rsc56Rsc56Rsc56Rsc56Rsc56Rsc56Rsc56Rsc56Rsc56Rsc56Rsc56Rsc56Rsc56Rsc56Rsc56Rsc56Rsc56Rsc56

Sth1

Sfh1

Rsc6Rsc6Rsc6Rsc6Rsc6Rsc6Rsc6Rsc6Rsc6Rsc6Rsc6Rsc6Rsc6Rsc6Rsc6Rsc6Rsc6Rsc6Rsc6Rsc6Rsc6Rsc6 Sth1Sth1

Sfh1Rsc9

Rsc6Rsc6Rsc6Rsc6Rsc6Rsc6Rsc6Rsc6Rsc6Rsc6Rsc6Rsc8/Rsc8/Rsc8/Rsc8/Rsc8/Rsc8/Rsc8/Swh3Swh3Swh3

Rsc9

Rsc6Rsc8/Rsc8/Rsc8/Rsc8/Rsc8/Rsc8/Rsc8/Rsc8/Rsc8/Rsc8/Rsc8/Rsc8/Rsc8/Rsc8/Rsc8/Rsc8/Rsc8/Rsc8/Swh3Swh3Swh3Swh3Swh3

Rsc9

Rsc6Rsc6Rsc6Rsc6Rsc6Rsc6Rsc6Rsc6Rsc6

Rsc4Rsc4Rsc4Rsc4Rsc4Rsc4Rsc4Rsc4Rsc4Rsc4Rsc4Rsc4Rsc4Rsc4Rsc4Rsc4Rsc4Rsc4Rsc4Rsc4Rsc4Rsc4Rsc4Rsc4Rsc4Rsc4Rsc4Rsc4Rsc4Rsc4Rsc4Rsc4Rsc4Rsc4Rsc4Rsc4Rsc4Rsc4Rsc4Rsc4Rsc4Rsc4Rsc4Rsc4Rsc4

Human BAF/PBAFHuman BAF/PBAFHuman BAF/PBAFHuman BAF/PBAF

Sfh1Rsc1or 2

BAP111/BAP111/BAP111/dalao

Fly BAP/PBAPFly BAP/PBAPFly BAP/PBAPFly BAP/PBAPFly BAP/PBAPFly BAP/PBAPFly BAP/PBAPFly BAP/PBAPFly BAP/PBAPFly BAP/PBAPFly BAP/PBAPFly BAP/PBAPFly BAP/PBAPFly BAP/PBAP

Pol II regulationPol II regulation

Fly BAP/PBAPFly BAP/PBAPFly BAP/PBAP

Pol II regulation

Cell-cycle/proliferationImmune system function




BAP111/BAP111/BAP111/dalao

BAP111/BAP111/BAP111/BAP111/BAP111/BAP111/BAP111/BAP111/BAP111/BAP111/BAP111/dalaodalao

BAP111/dalao

BAP60

Fly BAP/PBAPFly BAP/PBAPFly BAP/PBAPFly BAP/PBAPFly BAP/PBAPFly BAP/PBAPFly BAP/PBAPFly BAP/PBAPFly BAP/PBAPFly BAP/PBAPFly BAP/PBAPFly BAP/PBAP

BAF155/MOR

Cell-cycle/proliferation


BAF155/BAF155/BAF155/BAF155/BAF155/BAF155/BAF155/BAF155/MOR

BAF155/MOR

BAF53BAF53BAF53BAF53BAF53BAF53

-actin-actin-actin-actin-actin

PBAFPBAFPBAFImmune system functionCell-cycle/proliferationImmune system functionCell-cycle/proliferation

MORMOR

BAF155/BAF155/MOR

dalaodalaodalao

Brahma

Immune system function

dalaodalaodalao


dalaodalaodalaodalaodalaodalaodalaodalao


MORMOR

BAF155/BAF155/MOR

Brahma

Immune system function

Brahma

Cell-cycle/proliferationImmune system functionImmune system function

BrahmaBrahmaBrahmaBrahmaBrahmaBrahmaBrahmaBrahma


BAP60BAP60BAP60BAP60BAP60BAP60BAP60BAP60BAP60BAP60BAP60BAP60BAP60BAP60BAP60MORMOR

BAF155/BAF155/BAF155/BAF155/BAF155/BAF155/BAF155/MORMOR SNR1/

BAP45hSNF5/BAF47/

INI1

BAF60a,b,c

segregation, cohesion

nucleotide excision

Stem cell self-renewal/

nucleotide excision

Stem cell self-renewal/Stem cell self-renewal/

INI1

Stem cell self-renewal/

nucleotide excision nucleotide excision BAF155

BAF47/INI1

BAF47/BAF47/Stem cell self-renewal/ hSNF5/

BAF47/

BAF155BAF155

BAF170

BAF53BAF53BAF53BAF53a,ba,ba,ba,b

βββββ-actin-actin-actin-actin-actin-actin-actin-actin-actin

BAF47/INI1

hSNF5/BAF47/hSNF5/BAF47/BAF47/

INI1BAF47/BAF47/hSNF5/BAF47/

hBRM or BRG1

Human BAF/PBAFHuman BAF/PBAFHuman BAF/PBAFHuman BAF/PBAFHuman BAF/PBAFHuman BAF/PBAFHuman BAF/PBAFHuman BAF/PBAFHuman BAF/PBAFHuman BAF/PBAFHuman BAF/PBAFHuman BAF/PBAFHuman BAF/PBAFHuman BAF/PBAFHuman BAF/PBAFHuman BAF/PBAFHuman BAF/PBAFHuman BAF/PBAFHuman BAF/PBAFHuman BAF/PBAFHuman BAF/PBAFHuman BAF/PBAFHuman BAF/PBAFHuman BAF/PBAFHuman BAF/PBAFHuman BAF/PBAFHuman BAF/PBAFHuman BAF/PBAFHuman BAF/PBAFHuman BAF/PBAFHuman BAF/PBAFHuman BAF/PBAFHuman BAF/PBAFHuman BAF/PBAFHuman BAF/PBAFHuman BAF/PBAFHuman BAF/PBAFHuman BAF/PBAFHuman BAF/PBAFHuman BAF/PBAFHuman BAF/PBAFHuman BAF/PBAFHuman BAF/PBAFHuman BAF/PBAFHuman BAF/PBAFHuman BAF/PBAFHuman BAF/PBAFHuman BAF/PBAFHuman BAF/PBAFHuman BAF/PBAFHuman BAF/PBAFHuman BAF/PBAFHuman BAF/PBAFHuman BAF/PBAFHuman BAF/PBAFHuman BAF/PBAFHuman BAF/PBAFHuman BAF/PBAFHuman BAF/PBAFHuman BAF/PBAFHuman BAF/PBAFHuman BAF/PBAFHuman BAF/PBAFHuman BAF/PBAFHuman BAF/PBAFHuman BAF/PBAFHuman BAF/PBAFHuman BAF/PBAFHuman BAF/PBAF

BAF155BAF60BAF60a,b,ca,b,ca,b,ca,b,ca,b,c

BAF155BAF155

BAF170BAF170BAF170

BAF53BAF53BAF57BAF57BAF57BAF57BAF57BAF57BAF57BAF57BAF57

BAF60BAF60BAF60BAF60BAF60BAF60BAF60BAF60BAF60BAF60BAF60BAF60BAF60BAF60BAF60BAF60BAF60BAF60a,b,ca,b,ca,b,ca,b,ca,b,ca,b,ca,b,ca,b,ca,b,ca,b,ca,b,ca,b,c hBRM or hBRM or hBRM or hBRM or hBRM or hBRM or hBRM or hBRM or hBRM or hBRM or hBRM or hBRM or hBRM or hBRM or hBRM or hBRM or hBRM or hBRM or hBRM or

BRG1BRG1BRG1BRG1BRG1BRG1BRG1BRG1BRG1BRG1BRG1BRG1

BAF45a,b,c,d

Subunits with similar colors within a complex indicate functional modules, and identical colors between organisms denote related subunits.

DNA entry/exit points

Dyad axisPredicted translocase

binding site

Histone H3 tail

Unwrapping

S I T E E X P O S U R E

Repositioning

Octamer ejection

Dimer ejection

++

ATP ADP

Remodeler

DNA-binding protein

Nucleosome

The different outcomes of SWI/SNF chromatin remodeling

Model of the RSC-nucleosome complex

Sth1 conducts ATP-dependent DNA translocation

DNA is drawn from one side of the nucleosome and pumped toward the other

Disruption of histone-DNA contacts leads to remodeling outcomes (see below)

SnapShot: Chromatin Remodeling: SWI/SNFMargaret M. Kasten, Cedric R. Clapier, and Bradley R. CairnsHHMI, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USA

SWI/SNF-family complexes are large chromatin-remodeling machines that move or eject nucleosomes, providing proper nucleosome positioning and density at genes and other loci. The SWI/SNF complex was first discovered in yeast through a combination of genetic screens and biochemical purification. SWI/SNF was connected to chromatin/nucleosome function by genetic experiments (Winston and Carlson, 1992) and also through the biochemical reconstitution of nucleosome perturbation and sliding (Winston and Carlson, 1992; Narlikar et al., 2002). Genetic and biochemical experiments involving SWI/SNF-family complexes from flies, mice, and human cells have contributed greatly to our understanding of SWI/SNF remodelers, revealing them as essential and abundant machines needed for many chromosomal functions, transcription factor binding, proper gene regulation, and many aspects of development (Cairns and Clapier, 2009; Ho and Crabtree, 2010).

Composition and Functions of SWI/SNF-Family ComplexesSWI/SNF-family complexes are conserved in eukaryotes and all contain a DNA-dependent ATPase as their catalytic subunit and conserved associated proteins such as actin-related proteins and bromodomain-containing proteins, which bind acetylated lysines in histones and other proteins (Clapier and Cairns, 2009). However, each organism builds a slightly different set of SWI/SNF-related complexes, using both conserved proteins and also unique attendant subunits to help specialize each complex, depicted by arrows (i.e., BAF or PBAF complexes). A key recent feature (not depicted) for mammalian BAF complexes are their unique compositions in embryonic stem cells, and during developmental transitions, and evidence that they help guide developmental decisions (Ho and Crabtree, 2010). SWI/SNF-family complexes are diverse in function. SWI/SNF complexes regu-late chromatin structure at a large number of genes, impacting gene poising, transcription initiation, and transcript elongation (Clapier and Cairns, 2009). Many of their functions (colored text) relate to their transcriptional impact on particular genes, but they also have a direct role in other processes such as DNA repair (red text).

Current Structural ModelsThree groups have produced similar EM structures of the yeast SWI/SNF-family complex RSC—Remodels the Structure of Chromatin (Asturias et al., 2002; Leschziner et al., 2007; Skiniotis et al., 2007; Chaban et al., 2008), and two of SWI/SNF (or PBAF) complexes (Leschziner et al., 2005; Dechassa et al., 2008). Depicted is one such RSC structure (in gray) with the nucleosome modeled into the pocket (Leschziner et al., 2007). The pocket is of essentially perfect nucleosome dimension, with no steric clashes. The orientation of the nucleosome and the position of features (arrows) are speculative. The catalytic subunit is known to use ATP-dependent DNA translocation to break histone-DNA contacts and reposition nucleosomes, drawing in DNA from one side of the nucleosome and pumping it toward the other side (Clapier and Cairns, 2009). SWI/SNF-related complexes like RSC contain multiple histone-binding motifs (such as bromodomains) that recognize histone modifications, which may affect the affinity of the complex for nucleosomes or affect the outcome/mode of remodeling that occurs (see below).

The Different Outcomes of SWI/SNF Chromatin RemodelingMany DNA-binding factors (red oval) cannot bind DNA if their cognate site is on the nucleosome, an octamer of histone proteins consisting of two H2A/H2B dimers and an H3/H4 tetramer. SWI/SNF-family complexes affect the positioning and density of nucleosomes, which affect the access of DNA-binding factors to their cognate sites. Remodelers like SWI/SNF (dark blue disk) are targeted to particular nucleosomes (light blue spheres) either through histone modifications or through a “pioneering” DNA-binding protein (not depicted). The remodeler can then hydrolyze ATP to conduct one of many types of reactions, each of which can lead to site exposure for an additional DNA-binding protein (red oval). The DNA-binding protein can be a repressor, and activator, or a regulator of a chromosomal region—thus SWI/SNF complexes should be considered regulated nucleosome remodelers, rather than machinery dedicated to a particular process (for example, transcriptional activation).

RefeRences

Asturias FJ, Chung WH, Kornberg RD, Lorch Y. (2002) Structural analysis of the RSC chromatin-remodeling complex. Proc. Natl. Acad. Sci. USA, 99 13477-80.

Chaban, Y., Ezeokonkwo, C., Chung, W.H., Zhang, F., Kornberg, R.D., Maier-Davis, B., Lorch, Y., and Asturias, F.J. (2008). Structure of a RSC-nucleosome complex and insights into remodeling. Nat. Struct. Mol. Biol. 15, 1272–1277.

Clapier, C., and Cairns, B.R. (2009). The biology of chromatin remodeling complexes. Annu. Rev. Biochem. 78, 273–304.

Dechassa ML, Zhang B, Horowitz-Scherer R, Persinger J, Woodcock CL, Peterson CL, Bartholomew B.(2008) Architecture of the SWI/SNF-nucleosome complex. Mol Cell Biol. 28, 6010-21.

Ho, L., and Crabtree, G.R. (2010). Chromatin remodelling during development. Nature 463, 474–484.

Leschziner AE, Lemon B, Tjian R, Nogales E. (2005). Structural studies of the human PBAF chromatin-remodeling complex. Structure 13, 267-75.

Leschziner, A.E., Saha, A., Wittmeyer, J., Zhang, Y., Bustamante, C., Cairns, B.R., and Nogales, E. (2007). Conformational flexibility in the chromatin remodeler RSC observed by electron microscopy and the orthogonal tilt reconstruction method. Proc. Natl. Acad. Sci. USA 104, 4913–4918.

Narlikar GJ, Fan HY, Kingston RE. (2002) Cooperation between complexes that regulate chromatin structure and transcription. Cell 108, 475-87.

Skiniotis, G., Moazed, D., and Walz, T. (2007). Acetylated histone tail peptides induce structural rearrangements in the RSC chromatin remodeling complex. J. Biol. Chem. 282, 20804–20808.

Winston, F., and Carlson, M. (1992). Yeast SNF/SWI transcriptional activators and the SPT/SIN chromatin connection. Trends Genet. 8, 387–391.

310.e1 Cell 144, January 21, 2011 ©2011 Elsevier Inc. DOI 10.1016/j.cell.2011.01.007

snapshot: chromatin remodeling:swi/snf...snapshot: chromatin remodeling: swi/snf margaret m. kasten,...

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