Role of Histone H3 Lysine 9 Methylation in Epigenetic Control of Heterochromatin Assembly

Abstract

The assembly of higher order chromatin structures has been linked to the covalent modifications of histone tails. We provide in vivo evidence that lysine 9 of histone H3 (H3 Lys9) is preferentially methylated by the Clr4 protein at heterochromatin-associated regions in fission yeast. Both the conserved chromo- and SET domains of Clr4 are required for H3 Lys9 methylation in vivo. Localization of Swi6, a homolog of Drosophila HP1, to heterochomatic regions is dependent on H3 Lys9 methylation. Moreover, an H3-specific deacetylase Clr3 and a beta-propeller domain protein Rik1 are required for H3 Lys9 methylation by Clr4 and Swi6 localization. These data define a conserved pathway wherein sequential histone modifications establish a "histone code" essential for the epigenetic inheritance of heterochromatin assembly.

Gradual development of a genome‐wide H3‐K9 trimethylation pattern in paternally derived pig pronucleus

“…The species difference in development of the paternal H3-K9 methylation pattern might simply be due to the activity of certain histone methyltransferases (HMTases) in the oocyte cytoplasm. Various H3-K9-specific HMTases have been characterized to date, including SUVAR39 (Rea et al, 2000;Nakayama et al, 2001), G9A (Tachibana et al, 2002), GLP/ Eu-HMTase (Ogawa et al, 2002), SETDB1 (Schultz et al, 2002;Yang et al, 2002;Dodge et al, 2004), and SETDB2 (Mabuchi et al, 2001). Currently, however, it is unknown which activity, or combination of activities, is responsible for development of the paternal H3-m 3 K9 pattern in the pig and whether the activity responsible is absent from, or inhibited in, the mouse fertilized oocyte.…”

Lamr1 functional retroposon causes right ventricular dysplasia in mice

“…7e). HP1 is a key heterochromatin protein that regulates gene silencing by interacting with methylated histones 17 . HP1-α also localizes with DAPI-positive heterochromatin 18 .…”

Bop encodes a muscle-restricted protein containing MYND and SET domains and is essential for cardiac differentiation and morphogenesis

“…Covalent acetylation of specific lysine residues on histone tails by histone acetyltransferases (HATs) promotes chromatin relaxation and transcription, whereas deacetylation by histone deacetylases (HDACs) in a reverse reaction results in chromatin condensation and silencing of gene transcription [10][11][12] . Some chromatin remodeling proteins that share a highly conserved SET domain, originally described in the proteins su(var)-39, enhancer of zeste and trithorax, can methylate unacetylated lysine residues on histone tails, resulting in more permanent silencing of transcription [13][14] or, in some cases, activation of transcription 15 . No cardiac-specific function for proteins containing SET domains, however, has been described.…”