Polycomb in Transcriptional Phase Transition of Developmental Genes

Combinatorial associations between distinct chromatin domains, namely promoters and cis-regulatory elements, determine transcriptional status. Developmental regulatory gene expression, mostly regulated by the Polycomb/Trithorax group of chromatin regulators, is often temporally and spatially specific, and sometimes changes repeatedly within the same cell lineage. Dysregulated expression of these genes causes morphological and/or functional disorganization of tissues and organs. Therefore, maintenance of both the active and negative states of transcription is equally important. In this review, we summarize the mechanisms of transition between transcriptional status of developmental regulators, including complex processes for enhancer activation and promoter–enhancer association. In particular, we propose testable models in which Polycomb group factors contribute to promoter–enhancer associations and thus proper gene expression. Polycomb group factors form mainly two distinct protein complexes, Polycomb repressive complex (PRC)1 and PRC2; both of which are central players in transcriptional repression of developmental genes. PRCs are highly diversified and form many functionally different complexes. Particularly, PRC1 exists as at least six different stable complexes. Recent research supports a new model for PRC recruitment to chromatin, in which variant PRC1.1 initiates PRC recruitment and transcriptional repression. Emerging data show that PRCs are involved in regulation of higher-order chromatin organization, by which PRCs could contribute to both induced activation and repression of target gene transcription by regulating promoter–enhancer association. PRC1 subcomplexes could be differentially used to confer reversibility and robustness to PcG-dependent transcriptional regulation of developmental genes.