SET DOMAIN PROTEINS MODULATE CHROMATIN DOMAINS IN EU-CHROMATIN AND HETEROCHROMATIN

The SET domain is a 130-amino acid, evolutionarily conserved sequence motif present in chromosomal proteins that function in modulating gene activities from yeast to mammals. Initially identified as members of the Polycomb- and trithorax-group (Pc-G and trx-G) gene families, whic h are required to maintain expression boundaries of homeotic selector (HOM-C) genes, SET domain proteins are also involved in position-effec t-variegation (PEV), telomeric and centromeric gene silencing, and pos sibly in determining chromosome architecture. These observations impli cate SET domain proteins as multifunctional chromatin regulators with activities in both eu-and heterochromatin - a role consistent with the ir modular structure, which combines the SET domain with additional se quence motifs of either a cysteine-rich region/zinc-finger type or the chrome domain. Multiple functions for chromatin regulators are not re stricted to the SET protein family, since many trx-G (but only very fe w Pc-G) genes are also modifiers of PEV. Together, these data establis h a model in which the modulation of chromatin domains is mechanistica lly linked with the regulation of key developmental loci (e.g. HOM-C).