Molecular mechanisms of gene-specific transcriptional regulation by histone methyl transferase

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Heterochromatin is the fraction of genome that remains condensed throughout the cell cycle, replicates in the late S phase, and is generally associated with pericentric and telomeric regions of chromosomes. Euchromatic genes placed into proximity of heterochromatin by chromosomal rearrangement or trans-recruitment will be variably, silenced, a phenomenon known as position effect variegation (PEV). The Polycomb group protein (PcG)-mediated gene silencing has often been compared with the heterochromatin-mediated one because some conserved domains observed in PcG proteins are shared with HP1 (chromodomain) and Su(var)3-9 (chromodomain and SET domain), and also because PcG proteins, like modifiers of PEV, are dosage sensitive.In order to elucidate molecular mechanisms of heterochromatin initiation and/or maintenance by SUV39H1-HP1 and SU(Z)12-EZH2 systems, we investigated interactions of these proteins. We found that 1) self-interaction through the chromo shadow domain of HP1 is crucial for recruitment of SUV39H1 onto nucleosomes 2) PcG SU(Z)12 directly interacts with HP1 and EZH2 and represses transcription in the presence of HP1. We suggest that a role for SU(Z)12 in the maintenance of heterochromatin and/or HP1-mediated transcriptional repression of euchromatic genes by recruiting EZH2 or EED-EZH2 complex onto HP1□-bound nucleosomes.