DOI: 10.1126/science.1063127 , 1074 (2001); 293Science et al.Thomas Jenuwein,Translating the Histone Code www.sciencemag.org (this information is current as of March 17, 2008 ):The following resources related to this article are available online at http://www.sciencemag.org/cgi/content/full/293/5532/1074version of this article at: including high-resolution figures, can be found in the onlineUpdated information and services,found at: can berelated to this articleA list of selected additional articles on the Science Web sites http://www.sciencemag.org/cgi/content/full/293/5532/1074#related-content http://www.sciencemag.org/cgi/content/full/293/5532/1074#otherarticles, 30 of which can be accessed for free: cites 88 articlesThis article 2091 article(s) on the ISI Web of Science. cited byThis article has been http://www.sciencemag.org/cgi/content/full/293/5532/1074#otherarticles 95 articles hosted by HighWire Press; see: cited byThis article has been http://www.sciencemag.org/cgi/collection/molec_biolMolecular Biology : subject collectionsThis article appears in the following http://www.sciencemag.org/about/permissions.dtl in whole or in part can be found at: this articlepermission to reproduce of this article or about obtaining reprintsInformation about obtaining registered trademark of AAAS. is aScience2001 by the American Association for the Advancement of Science; all rights reserved. The title CopyrightAmerican Association for the Advancement of Science, 1200 New York Avenue NW, Washington, DC 20005. (print ISSN 0036-8075; online ISSN 1095-9203) is published weekly, except the last week in December, by theScience on March 17, 2008 www.sciencemag.orgDownloaded from69. Y. Habu, T. Kakutani, J. Paszkowski, Curr. Opin. Genet.Dev. 11, 215 (2001).70. M. Wassenegger, Plant Mol. Biol. 43, 203 (2000).71. M. A. Matzke, A. J. Matzke, J. M. Kooter, Science 293,1080 (2001).72. J. Bender, Trends Biochem. Sci. 23, 252 (1998).73. E. U. Selker, Cell 97, 157 (1999).74. M. N. Raizada, M. I. Benito, V. Walbot, Plant J. 25,79(2001).75. R. F. Ketting, T. H. Haverkamp, H. G. van Luenen, R. H.Plasterk, Cell 99, 133 (1999).76. H. Tabara et al., Cell 99, 123 (1999).77. B. H. Ramsahoye et al., Proc. Natl. Acad. Sci. U.S.A.97, 5237 (2000).78. P. Svoboda, P. Stein, H. Hayashi, R. M. Schultz, De-velopment 127, 4147 (2000).79. C. Cogoni et al., EMBO J. 15, 3153 (1996).80. G. Faugeron, Curr. Opin. Microbiol. 3, 144 (2000).81. L. Jackson-Grusby et al., Nature Genet. 27, 31 (2001).82. J. P. Vielle-Calzada, R. Baskar, U. Grossniklaus, Nature404, 91 (2000).83. P. S. Springer, D. R. Holding, A. Groover, C. Yordan,R. A. Martienssen, Development 127, 1815 (2000).84. J. P. Vielle-Calzada et al., Genes Dev. 13, 2971 (1999).85. R. Vinkenoog et al., Plant Cell 12, 2271 (2000).86. S. Adams, R. Vinkenoog, M. Spielman, H. G. Dickinson,R. J. Scott, Development 127, 2493 (2000).87. M. Byrne, M. Timmermans, C. Kidner, R. Martienssen,Curr. Opin. Plant Biol. 4, 38 (2001).88. E. B. Cambareri, R. Aisner, J. Carbon, Mol. Cell. Biol.18, 5465 (1998).89. P. SanMiguel et al., Science 274, 765 (1996).90. R. Mauricio, Nature Rev. Genet. 2, 370 (2001).91. P. Cubas, C. Vincent, E. Coen, Nature 401, 157 (1999).92. R. Martienssen, Curr. Opin. Genet. Dev. 8, 240(1998).93. Z. J. Chen, C. S. Pikaard, Genes Dev. 11, 2124 (1997).94. L. Comai et al., Plant Cell 12, 1551 (2000).95. H. S. Lee, Z. J. Chen, Proc. Natl. Acad. Sci. U.S.A. 98,6753 (2001).96. We thank E. Selker, E. Richards, V. Chandler, S. Kaep-pler, S. Jacobsen, and J. Bender for communicatingresults prior to publication, two anonymous refereesfor suggestions for improvement, and our colleaguesfor many interesting discussions. R.M. and V.C. re-ceive grant support from the NSF (DBI 1057338).REVIEWTranslating the Histone CodeThomas Jenuwein1and C. David Allis2Chromatin, the physiological template of all eukaryotic genetic information, issubject to a diverse array of posttranslational modifications that largelyimpinge on histone amino termini, thereby regulating access to the underly-ing DNA. Distinct histone amino-terminal modifications can generate syner-gistic or antagonistic interaction affinities for chromatin-associated proteins,which in turn dictate dynamic transitions between transcriptionally active ortranscriptionally silent chromatin states. The combinatorial nature of histoneamino-terminal modifications thus reveals a “histone code” that considerablyextends the information potential of the genetic code. We propose that thisepigenetic marking system represents a fundamental regulatory mechanismthat has an impact on most, if not all, chromatin-templated processes, withfar-reaching consequences for cell fate decisions and both normal and patho-logical development.Genomic DNA is the ultimate template of ourheredity. Yet despite the justifiable excitementover the human genome, many challenges re-main in understanding the regulation and trans-duction of genetic information (1). It is unclear,for example, why the number of protein-codinggenes in humans, now estimated at ⬃35,000,only doubles that of the fruit fly Drosophilamelanogaster. Is DNA alone then responsiblefor generating the full range of information thatultimately results in a complex eukaryotic or-ganism, such as ourselves?We favor the view that epigenetics, im-posed at the level of DNA-packaging proteins(histones), is a critical feature of a genome-wide mechanism of information storage andretrieval that is only beginning to be under-stood. We propose that a “histone code” ex-ists that may considerably extend the infor-mation potential of the genetic (DNA) code.We review emerging evidence that histoneproteins and their associated covalent modi-fications contribute to a mechanism that canalter chromatin structure, thereby leading toinherited differences in transcriptional “on-off ” states or to the stable propagation ofchromosomes by defining a specialized high-er order structure at centromeres. Under theassumption that a histone code exists, at leastin some form, we discuss potential mecha-nisms for how such a code is “read” andtranslated into biological functions.Throughout this review, we have chosenepigenetic phenomena and underlying mecha-nisms in two general categories: chromatin-based events leading to either gene activation orgene silencing. In particular, we center our dis-cussion on examples where differences in “on-off ” transcriptional states are reflected by dif-ferences in
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