Title:
Genetic approaches to understand molecular mechanisms underlying Polycomb repression

Haruhiko Koseki and Kyo-ichi Isono
RIKEN Center for Allergy and Immunology

Abstract:
First part of my talk will be focused on the mechanistic aspects of Polycomb group (PcG) gene products to mediate the repression of Hox cluster genes, which are well-known determinants for segment identity along the anterior-posterior axis. It is established PcG proteins mediate Hox repression by forming at least two distinct evolutionally conserved protein complexes, PRC1 and PRC2, which mediate histone H2A mono-ubiquitination (H2Aub1) and H3K27 trimethylation (H3K27me3), respectively. Genome-wide studies supported that this biochemical cascade is active. However, molecular mechanism to mediate the repression by PRC1 is still not clear since PRC1 can mediate the chromatin compaction in histone tail-independent manner and H2Aub1 deposition is not sufficient for the silencing. This implies that PRC1 uses some other mechanism for silencing. In this study, we focused on the role of Polycomb body for Polycomb silencing. PRC1 has been show to form subnuclear structure called “PcG body” in various tumor cells whilst its biological implication is yet known. In this study, we tackled this issue by combining genetic and imaging approaches. We found SAM domains of Polyhomeotic homologues mediate focal accumulation of PRC1 to form Polycomb body and condensation of Polycomb target genes.

References :
Li X et al. (2011) Mammalian Polycomblike Pcl2/Mtf2 is a novel regulatory component of PRC2 that can differentially modulate Polycomb activity at both the Hox gene cluster and at Cdkn2a genes. Mol Cell Biol.
Endoh M.et al. (2008) Polycomb group proteins Ring1A/B are functionally linked to the core transcriptional regulatory circuitry to maintain ES cell identity. Development 135:1513-1524.
Sharif J. et al. (2007) The SRA protein Np95 mediates epigenetic inheritance by recruiting Dnmt1 to methylated DNA. Nature 450:908-912.