See online version for legend and references454 Cell 144, February 4, 2011 ©2011 Elsevier Inc. DOI 10.1016/j.cell.2011.01.019

SnapShot: Chromatin Remodeling:ISWIAdam N. Yadon and Toshio TsukiyamaFred Hutchinson Cancer Research Center, Seattle, WA 98109, USA

General domain structure

DEXD ATPase HAND

Helicase SANT

SLIDE

Isw2

ACF CHRAC

Isw2 Isw1a Isw1b

Replication, transcription, andTy1 integration regulation1

Nucleosome assembly, transcription,and replication regulation5

Chromatin structure andtranscription regulation6

Chromatin structure andtranscription regulation7

Replication and transcription regulation9

Transcription regulation13 DNA replication and repair regulation14 Functions unknown Cell differentiation and

transcription regulation15 Functions unknown Functions unknown

Chromatin structure andcentromere maintenance10

Development and transcription regulation11

CERF

Functions unknown Heterochromatin formation and/or replication regulation12

Developmental cellular expansion and

nuclear divisions8Functions unknown

Transcription regulation2 Cell fate determination3 Transcription regulation4

Itc1

Isw2

NoRC WICH NURF

Nucleosome sliding

Histone replacement

ISWI-A ISWI-DWCRF

ACF1

SNF2H

WCRF180

SNF2H

ACFACF1 WICHRSF

p175

ACF1

ISWI

WSTF

ISWI

ISWI

RSF1

Isw1

Ioc3

NURF ISWI

NURF RSF CHR11 CHR17

CHRAC

Saccharomyces cerevisiae Caenorhabditis elegans

Drosophila melanogaster Arabidopsis thaliana

Xenopus laevisMammals

Biochemical Activities

Trypanosoma brucei

Itc1

Isw2Dpb4

Dls1 Ioc2Ioc4

Isw1

NURF1

Isw1

?

Isw1

ACF1

ISWI

ACF1

ISWI

?

CHR11

?

CHR17

NURF301

ISWI

ACF1

SNF2H

RSF1

SNF2H SNF2L

CECR2

ATP ADP

TIP5

SNF2H

WSTF

SNF2H SNF2L

BPTF

RbAp46/48

RbAp46/48

ISWI

p200p15

p21p70 p200

p17ISWI

p55

ISWI

ISWI

ATP ADP

+

Histones

NURF38NURF38CHRAC15

CHRAC15

CHRAC15

CHRAC15

CHRAC17

CHRAC17

CHRAC16

CHRAC16

454.e1 Cell 144, February 4, 2011 ©2011 Elsevier Inc. DOI 10.1016/j.cell.2011.01.019

SnapShot: Chromatin Remodeling:ISWIAdam N. Yadon and Toshio TsukiyamaFred Hutchinson Cancer Research Center, Seattle, WA 98109, USA

The imitation switch (ISWI) family of ATP-dependent chromatin-remodeling enzymes comprises highly conserved protein complexes that utilize the energy of ATP hydrolysis to slide nucleosomes along DNA and/or replace histones within nucleosomes. All ATP-dependent chromatin-remodeling complexes, including the ISWI family, contain a conserved catalytic DEXD ATPase domain and a helicase domain. However, the combination of three C-terminally located domains, known as HAND, SANT, and SLIDE, is unique to ISWI family members. The SANT domain (structurally related to the c-Myb DNA-binding domains) binds unmodified histone tails, the SLIDE (SANT-like ISWI domain) domain binds nucleosomal DNA near the dyad axis, and the HAND domain is implicated in both histone and DNA binding/recognition. Representative ISWI-containing protein complexes from multiple species are depicted in this SnapShot, with specific in vivo biological functions for each listed below.

Biological Functions of ISWI-Containing Complexes1. Replication, Transcription, and Ty Integration RegulationFacilitates replication fork progression through late-replicating regions; represses mRNA and cryptic noncoding RNA transcription by negatively regulating NFR size; required for the periodic integration pattern of the Ty1 retrotransposon.2. Transcription RegulationRepresses and activates transcription at a small number of loci and is implicated in transcription elongation and termination regulation.3. Cell Fate DeterminationPromotes the expression of vulval cell fates by antagonizing the transcriptional and chromatin-remodeling activities of complexes similar to Myb-MuvB/dREAM, NuRD, and Tip60/NuA4.4. Transcription RegulationDownregulates VSV expression sites.5. Nucleosome Assembly, Transcription, and Replication RegulationRequired for the establishment and/or maintenance of periodic nucleosome arrays that contributes to pericentric position-effect variegation (PEV) and heterochromatic Poly-comb-mediated transcriptional gene silencing; implicated in the regulation of S phase length/progression.6. Chromatin Structure and Transcription RegulationMaintains higher-order chromatin structure by mediating chromatin compaction; disrupts the enhancer-blocking function of Fab7 and SF1 while augmenting the function of Fab8; activates transcription of GAGA target genes and ecdysone-responsive genes and is a coactivator of Armadillo; regulates innate immunity by repressing transcription of JAK/STAT target genes.7. Chromatin Structure and Transcription RegulationInvolved in formation of silent heterochromatin by incorporating the histone variant H2Av, thus suppressing position-effect variegation (PEV).8. Developmental Cellular Expansion and Nuclear DivisionsNecessary for cell expansion during late-diploid (sporophytic) embryogenesis and mitotic nuclear divisions during haploid (gametophytic) phase.9. Replication and Transcription RegulationRequired for S phase progression and facilitates pericentromeric heterochromatin DNA replication; represses transcription of the vitamin D3 receptor-regulated genes in humans.10. Chromatin Structure and Centromere MaintenanceImplicated in chromatin assembly and actively supports the assembly of CENP-A chromatin in humans.11. Development and Transcription RegulationFunctions in neural tube formation and terminal differentiation of ovarian granulose cells through regulation of StAR gene expression in mice.12. Heterochromatin Formation and/or Replication RegulationTargeted to pericentromeric heterochromatin during early stages of chromosome condensation and DNA replication.13. Transcription RegulationInvolved in the transcriptional repression of ribosomal RNA genes.14. DNA Replication and Repair RegulationImplicated in heterochromatin DNA replication by binding PCNA in mice; necessary for cell survival following DNA damage by methyl methanesulfate (MMS); and facilitates a DNA damage response pathway by controlling histone H2A.Z function in mice.15. Cell Differentiation and Transcription RegulationPromotes neurite outgrowth and transcription of engrailed 1 and 2 in humans.

Acknowledgments

T.T. is funded by NIGMS. A.N.Y. was supported by a Developmental Biology Predoctoral Training Grant T32HD007183 from the National Institute of Child Health and Human Develop-ment.

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