Title:
Activation of repressed genes

Haruhiko Koseki
Developmental Genetics Group, RIKEN

Abstract:
Polycomb group ( Pc G) proteins, in general, mediate the repression of developmental regulators in a reversible manner and contribute to establish their spatiotemporally regulated expression domains. It is however poorly understood how genes repressed by Pc G are activated by developmental cues. In this study, we identified a critical role of a tissue-specific enhancer in removing Pc G from the promoter region by using the mouse Meis2 gene as a model. Meis2repression in early neural development depends on binding of RING1, an essential E3 component of Pc G, to its promoter (PRT), which is secured by its association of another RING1-binding site (RBS) at the 3 ‘ end of the Meis2 gene . In the prospective midbrain, a midbrain-specific enhancer (MBE) transiently associates with the PRT and 3 ‘ RBS forming a PRT/MBE/RBS tri-region interaction in a Ring1 dependent manner. Upon midbrain development, dissociation of the RBS region from the tri-region interaction together with its binding to Ring1 leaves active PRT/MBE engagement by releasing it from the Pc G-mediated repressive domain.  This study therefore demonstrates the role of a tissue-specific enhancer to evict Pc G from the promoter region and activate Pc G-repressed genes in a tissue- and stage-specific manner.