Role of histone H3 lysine 9 methylation in epigenetic control of heterochromatin assembly

The assembly of higher order chromatin structures has been Linked to the co valent modifications of histone tails. We provide in vivo evidence that lys ine 9 of histone H3 (H3 Lys(9)) is preferentially methylated by the Clr4 pr otein at heterochromatin-associated regions in fission yeast. Both the cons erved chromo- and SET domains of Clr4 are required for H3 Lys(9) methylatio n in vivo. Localization of Swi6, a homolog of Drosophila HP1, to heterochom atic regions is dependent on H3 Lysg methylation. Moreover, an H3-specific deacetylase Clr3 and a beta -propeller domain protein Rik1 are required for H3 Lys(9) methylation by Clr4 and Swi6 Localization. These data define a c onserved pathway wherein sequential histone modifications establish a "hist one code" essential for the epigenetic inheritance of heterochromatin assem bly.