Restricted epigenetic inheritance of H3K9 methylation
Inheritance of a covalent histone modification
Genomic DNA is the repository of all genetic information and is packaged into chromatin. Chromatin is also a repository of regulatory information in the form of covalent marks added to the histones that package the DNA. These marks can determine tissue- and organ-specific gene expression patterns, which must be transmitted to daughter cells to maintain their identity. Ragunathan et al. and Audergon et al. show that in fission yeast, a chromatin mark, like genetic information, can be inherited across many cell generations. The mark can be inherited independently of DNA sequence, DNA methylation, or RNA interference. Thus, histone marks constitute true epigenetic information.
Science, this issue 10.1126/science.1258699; see also p. 132
Abstract
Posttranslational histone modifications are believed to allow the epigenetic transmission of distinct chromatin states, independently of associated DNA sequences. Histone H3 lysine 9 (H3K9) methylation is essential for heterochromatin formation; however, a demonstration of its epigenetic heritability is lacking. Fission yeast has a single H3K9 methyltransferase, Clr4, that directs all H3K9 methylation and heterochromatin. Using releasable tethered Clr4 reveals that an active process rapidly erases H3K9 methylation from tethering sites in wild-type cells. However, inactivation of the putative histone demethylase Epe1 allows H3K9 methylation and silent chromatin maintenance at the tethering site through many mitotic divisions, and transgenerationally through meiosis, after release of tethered Clr4. Thus, H3K9 methylation is a heritable epigenetic mark whose transmission is usually countered by its active removal, which prevents the unauthorized inheritance of heterochromatin.
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Supplementary Material
Summary
Materials and Methods
Figs. S1 to S10
Tables S1 to S3
Reference (32)
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References and Notes
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Published In
Science
Volume 348 | Issue 6230
3 April 2015
3 April 2015
Copyright
Copyright © 2015, American Association for the Advancement of Science.
Submission history
Received: 1 September 2014
Accepted: 26 January 2015
Published in print: 3 April 2015
Acknowledgments
We thank I. Stancheva and the Allshire lab for valuable discussions; E. S. Choi for RNA-seq data; and S. Grewal, F. van Leeuwen, L. Bayne, Y. Shi, H. D. Madhani, T. Urano, and H. Watanabe for providing strains and materials. P.N.C.B.A. was supported by the Wellcome Trust 4 Year PhD program in Cell Biology (grant 093852). R.C.A. is supported by a Wellcome Trust Principal Research Fellowship (grant 095021), the EC-NOE-EpiGeneSys (grant HEALTH-F4-2010-257082), and core funding to the Wellcome Trust Centre for Cell Biology (grant 092076). RNA-seq data have been deposited with the National Center for Biotechnology Information Gene Expression Omnibus under accession code SRX689922.
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