Table Of ContentResults and Problems in Cell Differentiation
41
Series Editors
D. Richter, H. Tiedge
BrehonC.Laurent (Ed.)
Chromatin Dynamics
in Cellular Function
With14Figuresand1Table
123
BrehonC.Laurent,PhD
DepartmentofOncologicalSciences
MountSinaiSchoolofMedicine
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Contents
StructureandFunctionofProteinModulesinChromatinBiology
K.L.Yap,M.-M.Zhou . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . 1
2 HistoneLysineAcetylationRecognition
bytheBromodomain . . . . . . . . . . . . . . . . . . . . . . 2
3 HistoneLysineMethylationRecognition . . . . . . . . . . . 4
4 ChromosomalDNA/HistoneBinding . . . . . . . . . . . . . 8
5 ChromosomalProtein–ProteinInteractions . . . . . . . . . 11
6 Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15
7 FutureDirections . . . . . . . . . . . . . . . . . . . . . . . . 17
8 ConcludingRemarks . . . . . . . . . . . . . . . . . . . . . . 17
References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18
TheGenerationandRecognitionofHistoneMethylation
M.S.Torok,P.A.Grant . . . . . . . . . . . . . . . . . . . . . . . . . 25
1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . 25
2 TheNucleosomeandChromatinStructure . . . . . . . . . . 26
2.1 ChromatinDomains . . . . . . . . . . . . . . . . . . . . . . 27
2.2 HistoneModifications . . . . . . . . . . . . . . . . . . . . . 27
3 HistoneMethylation . . . . . . . . . . . . . . . . . . . . . . 28
3.1 LysineMethylation . . . . . . . . . . . . . . . . . . . . . . . 29
3.2 ArginineMethylation . . . . . . . . . . . . . . . . . . . . . . 31
3.3 HistoneDemethylation . . . . . . . . . . . . . . . . . . . . . 32
4 HistoneModificationBindingProteins . . . . . . . . . . . . 33
4.1 Chromodomains . . . . . . . . . . . . . . . . . . . . . . . . 33
4.2 TudorandMalignantBrainTumorDomains . . . . . . . . . 35
4.3 WD40Domain . . . . . . . . . . . . . . . . . . . . . . . . . 36
5 HistoneModificationCrosstalkwithMethylation . . . . . . 36
6 ConclusionsandFuturePerspectives . . . . . . . . . . . . . 38
References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39
VI Contents
HistoneUbiquitylationandtheRegulationofTranscription
M.A.Osley,A.B.Fleming,C.-F.Kao . . . . . . . . . . . . . . . . . . 47
1 RegulationofHistoneUbiquitylation . . . . . . . . . . . . . 47
1.1 TheUbiquitinConjugatingPathway . . . . . . . . . . . . . . 49
1.2 FactorsRegulatingHistoneUbquitylation . . . . . . . . . . 50
2 RelationshipBetweenHistoneH2BUbiquitylation
andHistoneH3Methylation . . . . . . . . . . . . . . . . . . 55
3 RoleofHistoneUbiquitylationinGeneExpression . . . . . . 57
3.1 UbiquitylatedH2B . . . . . . . . . . . . . . . . . . . . . . . 57
3.2 UbiquitylatedH2A . . . . . . . . . . . . . . . . . . . . . . . 63
3.3 UbiquitylatedH4 . . . . . . . . . . . . . . . . . . . . . . . . 65
4 AdditionalCellularRolesofUbiquitylatedHistones . . . . . 66
5 SummaryandPerspectives . . . . . . . . . . . . . . . . . . . 66
References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 67
HistoneDynamicsDuringTranscription:
ExchangeofH2A/H2BDimersandH3/H4Tetramers
DuringPolIIElongation
C.Thiriet,J.J.Hayes . . . . . . . . . . . . . . . . . . . . . . . . . . . 77
1 ABriefHistoryofChromatinandTranscription . . . . . . . 77
2 RNAPolymeraseActivityInducesHistoneExchange
withFreePools . . . . . . . . . . . . . . . . . . . . . . . . . 79
3 HistoneExchangeMaybeDuetoRNAPolIIElongation
ThroughNucleosomes . . . . . . . . . . . . . . . . . . . . . 80
4 ExchangeofH3/H4TetramersDuringTranscription . . . . . 82
5 H2A/H2BvsH3/H4Exchange . . . . . . . . . . . . . . . . . 83
6 Perspectives . . . . . . . . . . . . . . . . . . . . . . . . . . . 85
References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 87
TheRolesofChromatinRemodellingFactorsinReplication
A.Neves-Costa,P.Varga-Weisz. . . . . . . . . . . . . . . . . . . . . 91
1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . 91
2 HistoneModificationsandDNAReplication . . . . . . . . . 94
3 HistoneChaperonesandDNAReplication . . . . . . . . . . 94
4 ATP-DependentRemodellingFactors
andChromatinDynamicsinDNAReplication . . . . . . . . 97
4.1 Energy-DependentChromatinRemodellersHaveRoles
inDNARepair . . . . . . . . . . . . . . . . . . . . . . . . . 97
4.2 ISWIComplexesFacilitateDNAReplicationinChromatin . . 98
4.3 ISWIComplexeshaveRoles
intheReplicationofChromatinStructures . . . . . . . . . . 99
4.4 ISWIComplexesTargetReplicationSites . . . . . . . . . . . 100
5 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . 101
References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 101
Contents VII
ChromatinModificationsinDNARepair
A.J.Morrison,X.Shen . . . . . . . . . . . . . . . . . . . . . . . . . . 109
1 OverviewofChromatinModifications . . . . . . . . . . . . . 109
1.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . 109
1.2 ChromatinModifications . . . . . . . . . . . . . . . . . . . . 110
2 HistoneModificationsinDNARepair . . . . . . . . . . . . . 111
2.1 H2AandH2B . . . . . . . . . . . . . . . . . . . . . . . . . . 111
2.2 H3andH4 . . . . . . . . . . . . . . . . . . . . . . . . . . . . 114
3 Chromatin-ModifyingComplexesinDNARepair . . . . . . 115
3.1 Histone-ModifyingComplexes . . . . . . . . . . . . . . . . . 115
3.2 Chromatin-RemodelingComplexes . . . . . . . . . . . . . . 115
4 FutureDirections . . . . . . . . . . . . . . . . . . . . . . . . 117
4.1 AdditionalChromatinModifiersinDNARepair . . . . . . . 117
4.2 RecruitmentandFunctionofChromatinModifiers
inDNARepair . . . . . . . . . . . . . . . . . . . . . . . . . 118
4.3 ChromatinModificationsandCancer . . . . . . . . . . . . . 120
4.4 Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . 121
References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 121
MechanismsforNucleosomeMovement
byATP-dependentChromatinRemodelingComplexes
A.Saha,J.Wittmeyer,B.R.Cairns . . . . . . . . . . . . . . . . . . . 127
1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . 127
2 NucleosomeSpecialization . . . . . . . . . . . . . . . . . . . 128
3 TheNucleosome:ABiophysicalChallengeforRemodelers . 129
3.1 RemodelerFamilies:Discovery,Functions,andProperties. . 130
3.2 RemodelersElicitDNA-
and/orNucleosome-dependentATPaseActivity . . . . . . . 132
3.3 NucleosomeSlidingandAccessibility . . . . . . . . . . . . . 133
3.4 TheSWI/SNFandISWIRemodelers
areATP-dependentDirectionalDNATranslocases . . . . . . 134
4 RemodelersResembleDNAHelicases/Translocases . . . . . 135
4.1 DNATranslocationfromanInternalNucleosomalSite . . . . 136
4.2 Helicases/TranslocasesProvideModels
forDNATranslocationbyRemodelers. . . . . . . . . . . . . 137
4.3 ApplyingPrinciplesofTranslocases
toRemodelNucleosomes . . . . . . . . . . . . . . . . . . . . 138
4.4 DNATranslocationMayUnderlieDNATwisting . . . . . . . 141
5 ChromatinRemodeling
EnablesSpecializedBiologicalFunctions . . . . . . . . . . . 142
5.1 NucleosomeAssemblyandSpacing . . . . . . . . . . . . . . 142
VIII Contents
5.2 HistoneOctamerTransfer . . . . . . . . . . . . . . . . . . . 143
5.3 NucleosomeEjection . . . . . . . . . . . . . . . . . . . . . . 143
6 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . 144
References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 144
SubjectIndex . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 149
ResultsProblCellDiffer(41)
L.Brehon:ChromatinDynamicsinCellularFunction
DOI10.1007/010/Published online:17February2006
© Springer-VerlagBerlinHeidelberg2006
StructureandFunctionofProteinModules
inChromatinBiology
KyokoL.Yap·Ming-MingZhou((cid:1))
StructuralBiologyProgram,DepartmentofPhysiologyandBiophysics,
MountSinaiSchoolofMedicine,NewYorkUniversity,1425MadisonAvenue,
NewYork,NY10029-6574USA
[email protected]
Abstract Chromatin-mediated gene transcription or silencing is a dynamic process in
which binding of various proteins or protein complexes can displace nucleosomal his-
tones from DNA to relieve repression or drive the gene into a highly repressed, silent
state.CovalentmodificationstoDNAandhistonesassociatedwithchromatinstructural
change play a crucial role in transcriptional regulation, with particular modifications
on certain residues associated with a specific transcriptional outcome. In recent years
a number of structural domains have been identified within chromatin-associated pro-
teins,includingDNAorRNAbindingdomains,protein-proteininteractiondomainsand
domainsthatrecognizespecificcovalentmodificationstohistonetails.Inthisreviewwe
discussthestructuralfeaturesoftheseproteinmodulesandthefunctionalrolestheyplay
inchromatinbiology.
1
Introduction
Gene transcriptional regulation at the chromatin level is coordinated by
a number of proteins and protein complexes that interact with nucleosomal
DNA and histone proteins. The addition and removal of covalent modifica-
tions to chromatin allow for another level of transcriptional controlbeyond
thegeneticcode.Toattainthisgoal,oneneedstounderstandthemechanisms
underlying the regulation and transduction of genetic information. Grow-
ing evidence supports the view that a genome-wide epigenetic mechanism,
imposedatthelevelofgenomicDNA-packinghistoneproteinsthroughpost-
translational amino acid modifications including acetylation, methylation,
phosphorylation,andubiquitination, playsafundamentalroleincontrolling
thecapacityofthegenomeforinformationstorageandretrievalinresponse
to physiological and environmental stimuli, and for inheritable changes of
gene function and expression. Site- and state-specific modifications on cer-
tain amino acid residues within nucleosomal histones have been associated
with a specific transcriptional outcome, e.g. gene repression or activation.
Indeed, the “histone code hypothesis” (Strahl and Allis 2000; Turner 2002)
postulates that different combinations of modifications, either in combina-
