RRC ID 69997
Author George JJ, Oittinen M, Martin-Diaz L, Zapilko V, Iqbal S, Rintakangas T, Arrojo Martins FT, Niskanen H, Katajisto P, Kaikkonen MU, Viiri K.
Title Polycomb Repressive Complex 2 Regulates Genes Necessary for Intestinal Microfold Cell (M Cell) Development.
Journal Cell Mol Gastroenterol Hepatol
Abstract BACKGROUND & AIMS:Microfold cells (M cells) are immunosurveillance epithelial cells located in the Peyer's patches (PPs) in the intestine and are responsible for monitoring and transcytosis of antigens, microorganisms, and pathogens. Mature M cells use the receptor glycoprotein 2 (GP2) to aid in transcytosis. Recent studies have shown transcription factors, Spi-B and SRY-Box Transcription Factor 8 (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. Our aim was to understand the role of polycomb repressive complex 2 (PRC2) as an epigenetic regulator of M-cell development. Estrogen-related-receptor γ (Esrrg), identified as a PRC2-regulated gene, was studied in depth, in addition to its relationship with Spi-B and Sox8.
METHODS:Comparative chromatin immunoprecipitation and global run-on sequencing analysis of mouse intestinal organoids were performed in stem condition, enterocyte conditions, and receptor activator of nuclear factor κ B ligand-induced M-cell condition. Esrrg, which was identified as one of the PRC2-regulated transcription factors, was studied in wild-type mice and knocked out in intestinal organoids using guide RNA's. Sox8 null mice were used to study Esrrg and its relation to Sox8.
RESULTS:chromatin immunoprecipitation and global run-on sequencing analysis showed 12 novel PRC2 regulated transcription factors, PRC2-regulated Esrrg is a novel M-cell-specific transcription factor acting on a receptor activator of nuclear factor κB ligand-receptor activator of nuclear factor κB-induced nuclear factor-κB pathway, upstream of Sox8, and necessary but not sufficient for a mature M-cell marker of Gp2 expression.
CONCLUSIONS: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. Transcript profiling: the data have been deposited in the NCBI Gene Expression Omnibus database (GSE157629).
Volume 12(3)
Pages 873-889
Published 2021-1-1
DOI 10.1016/j.jcmgh.2021.05.014
PII S2352-345X(21)00103-X
PMID 34058415
PMC PMC8346665
MeSH Animals Biomarkers Cell Differentiation / genetics Epithelial Cells / metabolism* Gene Expression Profiling Gene Expression Regulation* Intestinal Mucosa / cytology* Intestinal Mucosa / immunology Intestinal Mucosa / metabolism* Mice NF-kappa B / metabolism Peyer's Patches / cytology* Peyer's Patches / immunology Peyer's Patches / metabolism* Polycomb Repressive Complex 2 / metabolism* RANK Ligand / metabolism Receptor Activator of Nuclear Factor-kappa B / metabolism Signal Transduction
DNA material CSII-CMV-MCS-IRES2-Bsd (RDB04385)