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Restricted epigenetic inheritance of H3K9 methylation

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Science  03 Apr 2015:
Vol. 348, Issue 6230, pp. 132-135
DOI: 10.1126/science.1260638

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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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