Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
Originally published in Science Express on 5 September 2002 Science 27 September 2002: Vol. 297. no. 5590, pp. 2232 - 2237
DOI: 10.1126/science.1076466
Establishment and Maintenance of a Heterochromatin Domain
Ira M. Hall,12*Gurumurthy D. Shankaranarayana,1*Ken-ichi Noma,1*Nabieh Ayoub,3Amikam Cohen,3Shiv I. S. Grewal12
The higher-order assembly of chromatin imposes
structural organization on the genetic information of eukaryotes and is
thoughtto be largely determined by posttranslational modification ofhistone tails. Here, we study a 20-kilobase silent domain at themating-type region of fission yeast as a model for heterochromatinformation. We find that, although histone H3 methylated at lysine9 (H3
Lys9) directly recruits heterochromatin protein Swi6/HP1,
the criticaldeterminant for H3 Lys9 methylation to spread
in cis and to be inherited through mitosisand meiosis is Swi6 itself.
We demonstrate that a centromere-homologousrepeat (cenH)
present at the silent mating-type region is sufficientfor
heterochromatin formation at an ectopic site, and that itsrepressive
capacity is mediated by components of the RNA interference(RNAi)
machinery. Moreover, cenH and the RNAi machinery cooperateto nucleate heterochromatin assembly at the endogenous mat
locusbut are dispensable for its subsequent inheritance. This workdefines sequential requirements for the initiation and propagationof
regional heterochromatic domains.
1 Cold Spring Harbor Laboratory,
2 Watson School of Biological Sciences, Post Office
Box 100, Cold Spring Harbor, NY 11724, USA.
3 Department of Molecular Biology, The Hebrew
University-Hadassah Medical School, Jerusalem, Israel 91010.
*
These authors contributed equally to this work.
To whom correspondence should be addressed. E-mail:
grewal{at}cshl.org
The editors suggest the following Related Resources on Science sites:
In Science Magazine
PERSPECTIVES
Thomas Jenuwein (27 September 2002) Science297 (5590), 2215.
[DOI: 10.1126/science.1077903] |Summary »|Full Text »|PDF »
THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Effect of 27nt Small RNA on Endothelial Nitric-Oxide Synthase Expression.
M.-X. Zhang, C. Zhang, Y. H. Shen, J. Wang, X.-N. Li, L. Chen, Y. Zhang, J. S. Coselli, and X. L. Wang (2008)
Mol. Biol. Cell
19, 3997-4005
|Abstract »|Full Text »|PDF »
Closed Chromatin Architecture Is Induced by an RNA Duplex Targeting the HIV-1 Promoter Region.
K. Suzuki, T. Juelich, H. Lim, T. Ishida, T. Watanebe, D. A. Cooper, S. Rao, and A. D. Kelleher (2008)
J. Biol. Chem.
283, 23353-23363
|Abstract »|Full Text »|PDF »
DXZ4 chromatin adopts an opposing conformation to that of the surrounding chromosome and acquires a novel inactive X-specific role involving CTCF and antisense transcripts.
An Argonaute Transports siRNAs from the Cytoplasm to the Nucleus.
S. Guang, A. F. Bochner, D. M. Pavelec, K. B. Burkhart, S. Harding, J. Lachowiec, and S. Kennedy (2008)
Science
321, 537-541
|Abstract »|Full Text »|PDF »
Tandem repeats upstream of the Arabidopsis endogene SDC recruit non-CG DNA methylation and initiate siRNA spreading.
Chp1-Tas3 Interaction Is Required To Recruit RITS to Fission Yeast Centromeres and for Maintenance of Centromeric Heterochromatin.
J. L. DeBeauchamp, A. Moses, V. J. P. Noffsinger, D. L. Ulrich, G. Job, A. M. Kosinski, and J. F. Partridge (2008)
Mol. Cell. Biol.
28, 2154-2166
|Abstract »|Full Text »|PDF »
PolIVb influences RNA-directed DNA methylation independently of its role in siRNA biogenesis.
R. A. Mosher, F. Schwach, D. Studholme, and D. C. Baulcombe (2008)
PNAS
105, 3145-3150
|Abstract »|Full Text »|PDF »
Analysis of Dynamic Changes in Post-translational Modifications of Human Histones during Cell Cycle by Mass Spectrometry.
D. Bonenfant, H. Towbin, M. Coulot, P. Schindler, D. R. Mueller, and J. van Oostrum (2007)
Mol. Cell. Proteomics
6, 1917-1932
|Abstract »|Full Text »|PDF »
RNAi-dependent H3K27 methylation is required for heterochromatin formation and DNA elimination in Tetrahymena.
Y. Liu, S. D. Taverna, T. L. Muratore, J. Shabanowitz, D. F. Hunt, and C. D. Allis (2007)
Genes & Dev.
21, 1530-1545
|Abstract »|Full Text »|PDF »
The Clr4 methyltransferase determines the subnuclear localization of the mating-type region in fission yeast.
J. Alfredsson-Timmins, F. Henningson, and P. Bjerling (2007)
J. Cell Sci.
120, 1935-1943
|Abstract »|Full Text »|PDF »
Programming Smooth Muscle Plasticity With Chromatin Dynamics.
I. Vaillant, S. Tutois, C. Cuvillier, I. Schubert, and S. Tourmente (2007)
Plant Cell Physiol.
48, 745-752
|Abstract »|Full Text »|PDF »
Interaction of Epe1 With the Heterochromatin Assembly Pathway in Schizosaccharomyces pombe.
S. Isaac, J. Walfridsson, T. Zohar, D. Lazar, T. Kahan, K. Ekwall, and A. Cohen (2007)
Genetics
175, 1549-1560
|Abstract »|Full Text »|PDF »
Np95 Is Implicated in Pericentromeric Heterochromatin Replication and in Major Satellite Silencing.
R. Papait, C. Pistore, D. Negri, D. Pecoraro, L. Cantarini, and I. M. Bonapace (2007)
Mol. Biol. Cell
18, 1098-1106
|Abstract »|Full Text »|PDF »
HP1 Binding to Chromatin Methylated at H3K9 Is Enhanced by Auxiliary Factors.
R. Eskeland, A. Eberharter, and A. Imhof (2007)
Mol. Cell. Biol.
27, 453-465
|Abstract »|Full Text »|PDF »
Concise Review: Epigenetic Mechanisms Contribute to Pluripotency and Cell Lineage Determination of Embryonic Stem Cells.
Q. Gan, T. Yoshida, O. G. McDonald, and G. K. Owens (2007)
Stem Cells
25, 2-9
|Abstract »|Full Text »|PDF »
Timing and Sequence Requirements Defined for Embryonic Maintenance of Imprinted DNA Methylation at Rasgrf1.
R. Holmes, Y. Chang, and P. D. Soloway (2006)
Mol. Cell. Biol.
26, 9564-9570
|Abstract »|Full Text »|PDF »
Interactions between the RNA Interference Effector Protein Ago1 and 14-3-3 Proteins: CONSEQUENCES FOR CELL CYCLE PROGRESSION.
C. Stoica, J. B. Carmichael, H. Parker, J. Pare, and T. C. Hobman (2006)
J. Biol. Chem.
281, 37646-37651
|Abstract »|Full Text »|PDF »
Human heterochromatin proteins form large domains containing KRAB-ZNF genes.
M. J. Vogel, L. Guelen, E. de Wit, D. P. Hupkes, M. Loden, W. Talhout, M. Feenstra, B. Abbas, A.-K. Classen, and B. van Steensel (2006)
Genome Res.
16, 1493-1504
|Abstract »|Full Text »|PDF »
Transcription and Evolutionary Dynamics of the Centromeric Satellite Repeat CentO in Rice.
H.-R. Lee, P. Neumann, J. Macas, and J. Jiang (2006)
Mol. Biol. Evol.
23, 2505-2520
|Abstract »|Full Text »|PDF »
Characterization of the piRNA Complex from Rat Testes.
N. C. Lau, A. G. Seto, J. Kim, S. Kuramochi-Miyagawa, T. Nakano, D. P. Bartel, and R. E. Kingston (2006)
Science
313, 363-367
|Abstract »|Full Text »|PDF »
Fission Yeast Cid12 Has Dual Functions in Chromosome Segregation and Checkpoint Control.
T. Z. Win, A. L. Stevenson, and S.-W. Wang (2006)
Mol. Cell. Biol.
26, 4435-4447
|Abstract »|Full Text »|PDF »
The assembly and maintenance of heterochromatin initiated by transgene repeats are independent of the RNA interference pathway in Mammalian cells..
F. Wang, N. Koyama, H. Nishida, T. Haraguchi, W. Reith, and T. Tsukamoto (2006)
Mol. Cell. Biol.
26, 4028-4040
|Abstract »|Full Text »|PDF »
Euchromatin and Pericentromeric Heterochromatin: Comparative Composition in the Tomato Genome.
Y. Wang, X. Tang, Z. Cheng, L. Mueller, J. Giovannoni, and S. D. Tanksley (2006)
Genetics
172, 2529-2540
|Abstract »|Full Text »|PDF »
Differential Effects of Heterochromatin Protein 1 Isoforms on Mitotic Chromosome Distribution and Growth in Dictyostelium discoideum.
Role of the silkworm argonaute2 homolog gene in double-strand break repair of extrachromosomal DNA.
H. Tsukioka, M. Takahashi, H. Mon, K. Okano, K. Mita, T. Shimada, J. M. Lee, Y. Kawaguchi, K. Koga, and T. Kusakabe (2006)
Nucleic Acids Res.
34, 1092-1101
|Abstract »|Full Text »|PDF »
Telomere elongation is under the control of the RNAi-based mechanism in the Drosophila germline.
M. Savitsky, D. Kwon, P. Georgiev, A. Kalmykova, and V. Gvozdev (2006)
Genes & Dev.
20, 345-354
|Abstract »|Full Text »|PDF »
Evolutionary-conserved telomere-linked helicase genes of fission yeast are repressed by silencing factors, RNAi components and the telomere-binding protein Taz1.
K. R. Hansen, P. T. Ibarra, and G. Thon (2006)
Nucleic Acids Res.
34, 78-88
|Abstract »|Full Text »|PDF »
Assembly of additional heterochromatin distinct from centromere-kinetochore chromatin is required for de novo formation of human artificial chromosome.
H. Nakashima, M. Nakano, R. Ohnishi, Y. Hiraoka, Y. Kaneda, A. Sugino, and H. Masumoto (2005)
J. Cell Sci.
118, 5885-5898
|Abstract »|Full Text »|PDF »
Intergenic Transcription Is Not Required in Th2 Cells to Maintain Histone Acetylation and Transcriptional Permissiveness at the Il4-Il13 Locus.
A. Baguet, X. Sun, T. Arroll, A. Krumm, and M. Bix (2005)
J. Immunol.
175, 8146-8153
|Abstract »|Full Text »|PDF »
The Clr7 and Clr8 Directionality Factors and the Pcu4 Cullin Mediate Heterochromatin Formation in the Fission Yeast Schizosaccharomyces pombe.
G. Thon, K. R. Hansen, S. P. Altes, D. Sidhu, G. Singh, J. Verhein-Hansen, M. J. Bonaduce, and A. J. S. Klar (2005)
Genetics
171, 1583-1595
|Abstract »|Full Text »|PDF »
Silencing of retrotransposons in Dictyostelium by DNA methylation and RNAi.
M. Kuhlmann, B. E. Borisova, M. Kaller, P. Larsson, D. Stach, J. Na, L. Eichinger, F. Lyko, V. Ambros, F. Soderbom, et al. (2005)
Nucleic Acids Res.
33, 6405-6417
|Abstract »|Full Text »|PDF »
Dicer-Dependent Turnover of Intergenic Transcripts from the Human {beta}-Globin Gene Cluster.
Double-Stranded RNA Induces Sequence-Specific Antiviral Silencing in Addition to Nonspecific Immunity in a Marine Shrimp: Convergence of RNA Interference and Innate Immunity in the Invertebrate Antiviral Response?.
J. Robalino, T. Bartlett, E. Shepard, S. Prior, G. Jaramillo, E. Scura, R. W. Chapman, P. S. Gross, C. L. Browdy, and G. W. Warr (2005)
J. Virol.
79, 13561-13571
|Abstract »|Full Text »|PDF »
The Arabidopsis HETEROCHROMATIN PROTEIN1 Homolog (TERMINAL FLOWER2) Silences Genes Within the Euchromatic Region but not Genes Positioned in Heterochromatin.
K. Nakahigashi, Z. Jasencakova, I. Schubert, and K. Goto (2005)
Plant Cell Physiol.
46, 1747-1756
|Abstract »|Full Text »|PDF »
Characterization of Dicer-deficient murine embryonic stem cells.
E. P. Murchison, J. F. Partridge, O. H. Tam, S. Cheloufi, and G. J. Hannon (2005)
PNAS
102, 12135-12140
|Abstract »|Full Text »|PDF »
Aberrant T cell differentiation in the absence of Dicer.
S. A. Muljo, K. M. Ansel, C. Kanellopoulou, D. M. Livingston, A. Rao, and K. Rajewsky (2005)
J. Exp. Med.
202, 261-269
|Abstract »|Full Text »|PDF »
Sum1p, the Origin Recognition Complex, and the Spreading of a Promoter-Specific Repressor in Saccharomyces cerevisiae.
P. J. Lynch, H. B. Fraser, E. Sevastopoulos, J. Rine, and L. N. Rusche (2005)
Mol. Cell. Biol.
25, 5920-5932
|Abstract »|Full Text »|PDF »
Drosophila argonaute-2 is required early in embryogenesis for the assembly of centric/centromeric heterochromatin, nuclear division, nuclear migration, and germ-cell formation.
A Rik1-associated, cullin-dependent E3 ubiquitin ligase is essential for heterochromatin formation.
P. J. Horn, J.-N. Bastie, and C. L. Peterson (2005)
Genes & Dev.
19, 1705-1714
|Abstract »|Full Text »|PDF »
A potential link between transgene silencing and poly(A) tails.
M. C. SIOMI, H. TSUKUMO, A. ISHIZUKA, T. NAGAMI, and H. SIOMI (2005)
RNA
11, 1004-1011
|Abstract »|Full Text »|PDF »
In Vivo HP1 Targeting Causes Large-Scale Chromatin Condensation and Enhanced Histone Lysine Methylation.
P. J. Verschure, I. van der Kraan, W. de Leeuw, J. van der Vlag, A. E. Carpenter, A. S. Belmont, and R. van Driel (2005)
Mol. Cell. Biol.
25, 4552-4564
|Abstract »|Full Text »|PDF »
Small Interfering RNAs That Trigger Posttranscriptional Gene Silencing Are Not Required for the Histone H3 Lys9 Methylation Necessary for Transgenic Tandem Repeat Stabilization in Neurospora crassa.
A. Chicas, E. C. Forrest, S. Sepich, C. Cogoni, and G. Macino (2005)
Mol. Cell. Biol.
25, 3793-3801
|Abstract »|Full Text »|PDF »
Disclosing hidden transcripts: Mouse natural sense-antisense transcripts tend to be poly(A) negative and nuclear localized.
H. Kiyosawa, N. Mise, S. Iwase, Y. Hayashizaki, and K. Abe (2005)
Genome Res.
15, 463-474
|Abstract »|Full Text »|PDF »
Chromatin and RNAi factors protect the C. elegans germline against repetitive sequences.
V. J.P. Robert, T. Sijen, J. van Wolfswinkel, and R. H.A. Plasterk (2005)
Genes & Dev.
19, 782-787
|Abstract »|Full Text »|PDF »
RNA Interference (RNAi)-Dependent and RNAi-Independent Association of the Chp1 Chromodomain Protein with Distinct Heterochromatic Loci in Fission Yeast.
V. J. Petrie, J. D. Wuitschick, C. D. Givens, A. M. Kosinski, and J. F. Partridge (2005)
Mol. Cell. Biol.
25, 2331-2346
|Abstract »|Full Text »|PDF »
Transcriptional silencing of a transgene by RNAi in the soma of C. elegans.
A. Grishok, J. L. Sinskey, and P. A. Sharp (2005)
Genes & Dev.
19, 683-696
|Abstract »|Full Text »|PDF »
Conserved Locus-Specific Silencing Functions of Schizosaccharomyces pombe sir2+.
L. L. Freeman-Cook, E. B. Gomez, E. J. Spedale, J. Marlett, S. L. Forsburg, L. Pillus, and P. Laurenson (2005)
Genetics
169, 1243-1260
|Abstract »|Full Text »|PDF »
Dicer-deficient mouse embryonic stem cells are defective in differentiation and centromeric silencing.
C. Kanellopoulou, S. A. Muljo, A. L. Kung, S. Ganesan, R. Drapkin, T. Jenuwein, D. M. Livingston, and K. Rajewsky (2005)
Genes & Dev.
19, 489-501
|Abstract »|Full Text »|PDF »
Elimination of Foreign DNA during Somatic Differentiation in Tetrahymena thermophila Shows Position Effect and Is Dosage Dependent.
Y. Liu, X. Song, M. A. Gorovsky, and K. M. Karrer (2005)
Eukaryot. Cell
4, 421-431
|Abstract »|Full Text »|PDF »
Global Effects on Gene Expression in Fission Yeast by Silencing and RNA Interference Machineries.
K. R. Hansen, G. Burns, J. Mata, T. A. Volpe, R. A. Martienssen, J. Bahler, and G. Thon (2005)
Mol. Cell. Biol.
25, 590-601
|Abstract »|Full Text »|PDF »
RDE-2 interacts with MUT-7 to mediate RNA interference in Caenorhabditis elegans.
B. B. J. Tops, H. Tabara, T. Sijen, F. Simmer, C. C. Mello, R. H. A. Plasterk, and R. F. Ketting (2005)
Nucleic Acids Res.
33, 347-355
|Abstract »|Full Text »|PDF »
From The Cover: RNA-dependent RNA polymerase is an essential component of a self-enforcing loop coupling heterochromatin assembly to siRNA production.
T. Sugiyama, H. Cam, A. Verdel, D. Moazed, and S. I. S. Grewal (2005)
PNAS
102, 152-157
|Abstract »|Full Text »|PDF »
A Dicer-like protein in Tetrahymena has distinct functions in genome rearrangement, chromosome segregation, and meiotic prophase.
Regulation of Swi6/HP1-dependent Heterochromatin Assembly by Cooperation of Components of the Mitogen-activated Protein Kinase Pathway and a Histone Deacetylase Clr6.
H. S. Kim, E. S. Choi, J. A Shin, Y. K. Jang, and S. D. Park (2004)
J. Biol. Chem.
279, 42850-42859
|Abstract »|Full Text »|PDF »
Lsh, an epigenetic guardian of repetitive elements.
J. Huang, T. Fan, Q. Yan, H. Zhu, S. Fox, H. J. Issaq, L. Best, L. Gangi, D. Munroe, and K. Muegge (2004)
Nucleic Acids Res.
32, 5019-5028
|Abstract »|Full Text »|PDF »
cis-Acting Determinants of Heterochromatin Formation on Drosophila melanogaster Chromosome Four.
F.-L. Sun, K. Haynes, C. L. Simpson, S. D. Lee, L. Collins, J. Wuller, J. C. Eissenberg, and S. C. R. Elgin (2004)
Mol. Cell. Biol.
24, 8210-8220
|Abstract »|Full Text »|PDF »
Argonaute2 Is the Catalytic Engine of Mammalian RNAi.
J. Liu, M. A. Carmell, F. V. Rivas, C. G. Marsden, J. M. Thomson, J.-J. Song, S. M. Hammond, L. Joshua-Tor, and G. J. Hannon (2004)
Science
305, 1437-1441
|Abstract »|Full Text »|PDF »
Effects of Length and Location on the Cellular Response to Double-Stranded RNA.
Q. Wang and G. G. Carmichael (2004)
Microbiol. Mol. Biol. Rev.
68, 432-452
|Abstract »|Full Text »|PDF »
RNA-Mediated Programming of Developmental Genome Rearrangements in Paramecium tetraurelia.
O. Garnier, V. Serrano, S. Duharcourt, and E. Meyer (2004)
Mol. Cell. Biol.
24, 7370-7379
|Abstract »|Full Text »|PDF »
A Large Imprinted microRNA Gene Cluster at the Mouse Dlk1-Gtl2 Domain.
H. Seitz, H. Royo, M.-L. Bortolin, S.-P. Lin, A. C. Ferguson-Smith, and J. Cavaille (2004)
Genome Res.
14, 1741-1748
|Abstract »|Full Text »|PDF »
RNAi-dependent and RNAi-independent mechanisms contribute to the silencing of RIPed sequences in Neurospora crassa.
A. Chicas, C. Cogoni, and G. Macino (2004)
Nucleic Acids Res.
32, 4237-4243
|Abstract »|Full Text »|PDF »
"siRNAs and miRNAs": A meeting report on RNA silencing.
Z. HE and E. J. SONTHEIMER (2004)
RNA
10, 1165-1173
|Full Text »|PDF »
Dissection of a Natural RNA Silencing Process in the Drosophila melanogaster Germ Line.
A. A. Aravin, M. S. Klenov, V. V. Vagin, F. Bantignies, G. Cavalli, and V. A. Gvozdev (2004)
Mol. Cell. Biol.
24, 6742-6750
|Abstract »|Full Text »|PDF »
Lack of homologous sequence-specific DNA methylation in response to stable dsRNA expression in mouse oocytes.
P. Svoboda, P. Stein, W. Filipowicz, and R. M. Schultz (2004)
Nucleic Acids Res.
32, 3601-3606
|Abstract »|Full Text »|PDF »
RNAi-Independent Heterochromatin Nucleation by the Stress-Activated ATF/CREB Family Proteins.