Microfold cells (M cells) are immunosurveillance epithelial cells located in the Peyer's patches (PP's) in the intestine responsible for monitoring and transcytosis of antigens, microorganisms and pathogens. Mature Microfold cells employ the receptor Glyoprotein 2 (Gp2) to aid in transcytosis. Recent studies have revealed transcription factors, Spi-B and Sox8 are necessary for M cell differentiation but not sufficient. An exhaustive set of factors sufficient for differentiation and development of a mature Gp2+ M cell remains elusive AIM: To understand the role of polycomb repressive complex 2 (PRC2) as an epigenetic regulator of M cell development. Estrogen related receptor gamma (Esrrg) identified as a PRC2 regulated gene was studied in depth and it's relation to Spi-B and Sox8 METHODS: Comparitive Chip and Gro-seq analysis of mouse intestinal organoids were performed in stem condition, enterocyte condition and RankL induced M cell condition. Esrrg which was identified as one of the PRC2 regulated transcription factors (TF's) was studied in wildtype (WT) mice and knocked out in intestinal organoids using Crispr Cas9. Sox8 null mice was used to study Esrrg and its relation to Sox8 RESULTS: Chip and Gro-seq analysis revealed 12 novel PRC2 regulated transcription factors, PRC2 regulated Esrrg is a novel M cell specific transcription factor acting on a RankL-Rank induced NF-kB pathway, upstream of Sox8 and necessary but not sufficient for a mature M cell marker Gp2 expression CONCLUSION: PRC2 regulates a significant set of genes in M cells including Esrrg which is critical for M cell development and differentiation. Loss of Esrrg led to an immature M cell phenotype lacking in Sox8 and Gp2 expression.