IDENTIFICATION AND VALIDATION OF A PUTATIVE POLYCOMB RESPONSIVE ELEMENT IN THE HUMAN GENOME.

Identification and Validation of a Putative Polycomb Responsive Element in the Human Genome.

Identification and Validation of a Putative Polycomb Responsive Element in the Human Genome.

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Epigenetic cellular memory mechanisms that involve polycomb and trithorax group of proteins are well conserved across metazoans.The cis-acting elements interacting with these proteins, however, are poorly understood in mammals.In a directed search we identified a potential polycomb responsive element with 25 repeats of YY1 binding motifthatwe designate PRE-PIK3C2B as it occurs in the first intron of human PIK3C2B gene.It down regulates reporter gene expression in HEK cells and the Clothing - Womens Bottoms - Shorts repression is dependent on polycomb group of proteins (PcG).

We demonstrate that PRE-PIK3C2B interacts directly with YY1 in vitro and recruits PRC2 complex in vivo.The localization of PcG proteins including YY1 to PRE-PIK3C2B in HEK cells is decreased on knock-down Socks of either YY1 or SUZ12.Endogenous PRE-PIK3C2B shows bivalent marking having H3K27me3 and H3K4me3 for repressed and active state respectively.In transgenic Drosophila, PRE-PIK3C2B down regulates mini-white expression, exhibits variegation and pairing sensitive silencing (PSS), which has not been previously demonstrated for mammalian PRE.

Taken together, our results strongly suggest that PRE-PIK3C2B functions as a site of interaction for polycomb proteins.

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