Methylation/phosphorylation neighboring switch

Heterochromatin contains predominantly transcriptionally silent genes and includes specialized chromosome structures such as centromers and telomeres. It has been recognized during most of the cell cycle, heterochromatin protein 1 (HP1) is concentrated in heterochromatin, but with the onset of chromosome condensation at metaphase, much of HP1 leaves the chromatin.

It has been also known that tri-methylation of the lysine at the ninth position in the tails of histone H3 (H3K9me3) is important for recruiting HP1 to discrete regions of the chromosome, thereby regulating gene expression and heterochromatin formation. Fischle et al. (2005) found that phosphorylation of the serine at the tenth position of histone H3 (H3S10ph) can reverse the recruitment of HP1, causing the dissociation of HP1 from the chromatin at metaphase.

This binary 'methyl/phos switching' permits dynamic control of the HP1-H3K9me3 interaction, resulting the formation of heterochromatin. Unlike the dissociation of HP1 from the chromatin by the demetylation of lysine 9, this switch allow H3 to maintain methylation pattern. Fischle et al. reason:
"Stable transmission of the heterochromatin-defining H3K9me3 mark is needed accurately convey, from one cell generation to the next, which regions of the genome are supposed to be permanently silenced. If removal of HP1 from M-phase chromatin were accomplished by H3K9me3-erasing demethylase activity, the epigenetic information underlying this mark-and effector-system would have to be accurately re-established at the end of every cell cycle."


Hiroshi Izumi