The FUN30 Chromatin Remodeler, Fft3, Protects Centromeric and Subtelomeric Domains from Euchromatin Formation
The chromosomes of eukaryotes are organized into structurally and functionally discrete domains. This implies the presence of insulator elements that separate adjacent domains, allowing them to maintain different chromatin structures. We show that the Fun30 chromatin remodeler, Fft3, is essential for maintaining a proper chromatin structure at centromeres and subtelomeres. Fft3 is localized to insulator elements and inhibits euchromatin assembly in silent chromatin domains. In its absence, euchromatic histone modifications and histone variants invade centromeres and subtelomeres, causing a mis-regulation of gene expression and severe chromosome segregation defects. Our data strongly suggest that Fft3 controls the identity of chromatin domains by protecting these regions from euchromatin assembly.
Vyšlo v časopise:
The FUN30 Chromatin Remodeler, Fft3, Protects Centromeric and Subtelomeric Domains from Euchromatin Formation. PLoS Genet 7(3): e32767. doi:10.1371/journal.pgen.1001334
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.pgen.1001334
Souhrn
The chromosomes of eukaryotes are organized into structurally and functionally discrete domains. This implies the presence of insulator elements that separate adjacent domains, allowing them to maintain different chromatin structures. We show that the Fun30 chromatin remodeler, Fft3, is essential for maintaining a proper chromatin structure at centromeres and subtelomeres. Fft3 is localized to insulator elements and inhibits euchromatin assembly in silent chromatin domains. In its absence, euchromatic histone modifications and histone variants invade centromeres and subtelomeres, causing a mis-regulation of gene expression and severe chromosome segregation defects. Our data strongly suggest that Fft3 controls the identity of chromatin domains by protecting these regions from euchromatin assembly.
Zdroje
1. CamHP
SugiyamaT
ChenES
ChenX
FitzGeraldPC
2005
Comprehensive analysis of heterochromatin- and RNAi-mediated epigenetic control of the fission yeast genome.
Nat Genet
37
809
819
2. NomaK
AllisCD
GrewalSI
2001
Transitions in distinct histone H3 methylation patterns at the heterochromatin domain boundaries.
Science
293
1150
1155
3. BuchananL
Durand-DubiefM
RoguevA
SakalarC
WilhelmB
2009
The Schizosaccharomyces pombe JmjC-protein, Msc1, prevents H2A.Z localization in centromeric and subtelomeric chromatin domains.
PLoS Genet
5
e1000726
doi:10.1371/journal.pgen.1000726
4. HebbesTR
ClaytonAL
ThorneAW
Crane-RobinsonC
1994
Core histone hyperacetylation co-maps with generalized DNase I sensitivity in the chicken beta-globin chromosomal domain.
EMBO J
13
1823
1830
5. BraunsteinM
RoseAB
HolmesSG
AllisCD
BroachJR
1993
Transcriptional silencing in yeast is associated with reduced nucleosome acetylation.
Genes Dev
7
592
604
6. NomaK
SugiyamaT
CamH
VerdelA
ZofallM
2004
RITS acts in cis to promote RNA interference-mediated transcriptional and post-transcriptional silencing.
Nat Genet
36
1174
1180
7. DormanER
BusheyAM
CorcesVG
2007
The role of insulator elements in large-scale chromatin structure in interphase.
Semin Cell Dev Biol
18
682
690
8. OkiM
ValenzuelaL
ChibaT
ItoT
KamakakaRT
2004
Barrier proteins remodel and modify chromatin to restrict silenced domains.
Mol Cell Biol
24
1956
1967
9. DhillonN
RaabJ
GuzzoJ
SzyjkaSJ
GangadharanS
2009
DNA polymerase epsilon, acetylases and remodellers cooperate to form a specialized chromatin structure at a tRNA insulator.
EMBO J
28
2583
2600
10. IshiiK
AribG
LinC
Van HouweG
LaemmliUK
2002
Chromatin boundaries in budding yeast: the nuclear pore connection.
Cell
109
551
562
11. NomaK
CamHP
MaraiaRJ
GrewalSI
2006
A role for TFIIIC transcription factor complex in genome organization.
Cell
125
859
872
12. WoodV
GwilliamR
RajandreamMA
LyneM
LyneR
2002
The genome sequence of Schizosaccharomyces pombe.
Nature
415
871
880
13. ScottKC
MerrettSL
WillardHF
2006
A heterochromatin barrier partitions the fission yeast centromere into discrete chromatin domains.
Curr Biol
16
119
129
14. ScottKC
WhiteCV
WillardHF
2007
An RNA polymerase III-dependent heterochromatin barrier at fission yeast centromere 1.
PLoS ONE
2
e1099
doi:10.1371/journal.pone.0001099
15. OkiM
KamakakaRT
2005
Barrier function at HMR.
Mol Cell
19
707
716
16. LanF
ZaratieguiM
VillenJ
VaughnMW
VerdelA
2007
S. pombe LSD1 homologs regulate heterochromatin propagation and euchromatic gene transcription.
Mol Cell
26
89
101
17. ThonG
BjerlingP
BunnerCM
Verhein-HansenJ
2002
Expression-state boundaries in the mating-type region of fission yeast.
Genetics
161
611
622
18. OuspenskiII
ElledgeSJ
BrinkleyBR
1999
New yeast genes important for chromosome integrity and segregation identified by dosage effects on genome stability.
Nucleic Acids Res
27
3001
3008
19. TakahashiK
ChenES
YanagidaM
2000
Requirement of Mis6 centromere connector for localizing a CENP-A-like protein in fission yeast.
Science
288
2215
2219
20. TakahashiK
YamadaH
YanagidaM
1994
Fission yeast minichromosome loss mutants mis cause lethal aneuploidy and replication abnormality.
Mol Biol Cell
5
1145
1158
21. ClarkeL
AmstutzH
FishelB
CarbonJ
1986
Analysis of centromeric DNA in the fission yeast Schizosaccharomyces pombe.
Proc Natl Acad Sci U S A
83
8253
8257
22. ChikashigeY
KinoshitaN
NakasekoY
MatsumotoT
MurakamiS
1989
Composite motifs and repeat symmetry in S. pombe centromeres: direct analysis by integration of NotI restriction sites.
Cell
57
739
751
23. NakayamaJ
RiceJC
StrahlBD
AllisCD
GrewalSI
2001
Role of histone H3 lysine 9 methylation in epigenetic control of heterochromatin assembly.
Science
292
110
113
24. PartridgeJF
BorgstromB
AllshireRC
2000
Distinct protein interaction domains and protein spreading in a complex centromere.
Genes Dev
14
783
791
25. AllshireRC
JaverzatJP
RedheadNJ
CranstonG
1994
Position effect variegation at fission yeast centromeres.
Cell
76
157
169
26. BiX
YuQ
SandmeierJJ
ZouY
2004
Formation of boundaries of transcriptionally silent chromatin by nucleosome-excluding structures.
Mol Cell Biol
24
2118
2131
27. WirenM
SilversteinRA
SinhaI
WalfridssonJ
LeeHM
2005
Genomewide analysis of nucleosome density histone acetylation and HDAC function in fission yeast.
EMBO J
24
2906
2918
28. LantermannAB
StraubT
StralforsA
YuanGC
EkwallK
2010
Schizosaccharomyces pombe genome-wide nucleosome mapping reveals positioning mechanisms distinct from those of Saccharomyces cerevisiae.
Nat Struct Mol Biol
17
251
257
29. GarciaJF
DumesicPA
HartleyPD
El-SamadH
MadhaniHD
2010
Combinatorial, site-specific requirement for heterochromatic silencing factors in the elimination of nucleosome-free regions.
Genes Dev
24
1758
1771
30. UdvardyA
MaineE
SchedlP
1985
The 87A7 chromomere. Identification of novel chromatin structures flanking the heat shock locus that may define the boundaries of higher order domains.
J Mol Biol
185
341
358
31. ChungJH
WhiteleyM
FelsenfeldG
1993
A 5′ element of the chicken beta-globin domain serves as an insulator in human erythroid cells and protects against position effect in Drosophila.
Cell
74
505
514
32. NasmythKA
1982
The regulation of yeast mating-type chromatin structure by SIR: an action at a distance affecting both transcription and transposition.
Cell
30
567
578
33. KanohJ
SadaieM
UranoT
IshikawaF
2005
Telomere binding protein Taz1 establishes Swi6 heterochromatin independently of RNAi at telomeres.
Curr Biol
15
1808
1819
34. CooperJP
NimmoER
AllshireRC
CechTR
1997
Regulation of telomere length and function by a Myb-domain protein in fission yeast.
Nature
385
744
747
35. FischerT
CuiB
DhakshnamoorthyJ
ZhouM
RubinC
2009
Diverse roles of HP1 proteins in heterochromatin assembly and functions in fission yeast.
Proc Natl Acad Sci U S A
106
8998
9003
36. MotamediMR
HongEJ
LiX
GerberS
DenisonC
2008
HP1 proteins form distinct complexes and mediate heterochromatic gene silencing by nonoverlapping mechanisms.
Mol Cell
32
778
790
37. HorvathJE
BaileyJA
LockeDP
EichlerEE
2001
Lessons from the human genome: transitions between euchromatin and heterochromatin.
Hum Mol Genet
10
2215
2223
38. KellumR
SchedlP
1991
A position-effect assay for boundaries of higher order chromosomal domains.
Cell
64
941
950
39. GyurkovicsH
GauszJ
KummerJ
KarchF
1990
A new homeotic mutation in the Drosophila bithorax complex removes a boundary separating two domains of regulation.
EMBO J
9
2579
2585
40. GerasimovaTI
ByrdK
CorcesVG
2000
A chromatin insulator determines the nuclear localization of DNA.
Mol Cell
6
1025
1035
41. YusufzaiTM
TagamiH
NakataniY
FelsenfeldG
2004
CTCF tethers an insulator to subnuclear sites, suggesting shared insulator mechanisms across species.
Mol Cell
13
291
298
42. IwasakiO
TanakaA
TanizawaH
GrewalSI
NomaK
2010
Centromeric localization of dispersed Pol III genes in fission yeast.
Mol Biol Cell
21
254
265
43. Neves-CostaA
WillWR
VetterAT
MillerJR
Varga-WeiszP
2009
The SNF2-family member Fun30 promotes gene silencing in heterochromatic loci.
PLoS ONE
4
e8111
doi:10.1371/journal.pone.0008111
44. YusufzaiTM
FelsenfeldG
2004
The 5′-HS4 chicken beta-globin insulator is a CTCF-dependent nuclear matrix-associated element.
Proc Natl Acad Sci U S A
101
8620
8624
45. OhbaT
NishijimaH
NishitaniH
NishimotoT
2008
Schizosaccharomyces pombe Snf2SR, a novel SNF2 family protein, interacts with Ran GTPase and modulates both RanGEF and RanGAP activities.
Genes Cells
13
571
582
46. RoguevA
BandyopadhyayS
ZofallM
ZhangK
FischerT
2008
Conservation and rewiring of functional modules revealed by an epistasis map in fission yeast.
Science
322
405
410
47. AdraCN
DonatoJL
BadovinacR
SyedF
KherajR
2000
SMARCAD1, a novel human helicase family-defining member associated with genetic instability: cloning, expression, and mapping to 4q22-q23, a band rich in breakpoints and deletion mutants involved in several human diseases.
Genomics
69
162
173
48. SoininenR
SchoorM
HenselingU
TepeC
Kisters-WoikeB
1992
The mouse Enhancer trap locus 1 (Etl-1): a novel mammalian gene related to Drosophila and yeast transcriptional regulator genes.
Mech Dev
39
111
123
49. XueY
HaasSA
BrinoL
GusnantoA
ReimersM
2004
A DNA microarray for fission yeast: minimal changes in global gene expression after temperature shift.
Yeast
21
25
39
50. Durand-DubiefM
EkwallK
2009
Chromatin immunoprecipitation using microarrays.
Methods Mol Biol
529
279
295
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Genetika Reprodukčná medicínaČlánok vyšiel v časopise
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