Martins, F. T. A. | bioRxiv Science

bioRxiv2020

Polycomb Repressive Complex 2-controlled Essrg regulates intestinal Microfold cell differentiation.

Microfold cells (M cells) are immunosurveillance epithelial cells located in the Peyers patches in the intestine responsible for monitoring and transcytosis of antigens, microorganisms and pathogens. Many transcription factors, e.g., Spi-B and Sox8, necessary to M cell differentiation have been described but the exhaustive set of factors sufficient for differentiation and development of a mature M cell remains elusive. Moreover, the role of polycomb repressive complex 2 (PRC2) as an epigenetic regulator of M cell development has not yet been interrogated. Here, we show that PRC2 regulates a significant set of genes during the M cell differentiation including many transcription factors. Estrogen related receptor gamma (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. To conclude, with the aid of PRC2 target survey we identified the list of developmental genes specifically implicated in M cell development and Essrg as a necessary factor for Sox8-mediated M cell differentiation.

molecular biology↗

bioRxiv2020

Spectrum of genes for inherited hearing loss in the Israeli Jewish population, including the novel human deafness gene ATOH1

Mutations in more than 150 genes are responsible for inherited hearing loss, with thousands of different, severe causal alleles that vary among populations. The Israeli Jewish population includes communities of diverse geographic origins, revealing a wide range of deafness-associated variants and enabling clinical characterization of the associated phenotypes. Our goal was to identify the genetic causes of inherited hearing loss in this population, and to determine relationships among genotype, phenotype, and ethnicity. Genomic DNA samples from informative relatives of 88 multiplex families, all of self-identified Jewish ancestry, with either non-syndromic or syndromic hearing loss, were sequenced for known and candidate deafness genes using the HEar-Seq gene panel. The genetic causes of hearing loss were identified for 60% of the families. One gene was encountered for the first time in human hearing loss: ATOH1 (Atonal), a basic helix-loop-helix transcription factor responsible for autosomal dominant progressive hearing loss in a five-generation family. Our results demonstrate that genomic sequencing with a gene panel dedicated to hearing loss is effective for genetic diagnoses in a diverse population. Comprehensive sequencing enables well-informed genetic counseling and clinical management by medical geneticists, otolaryngologists, audiologists, and speech therapists and can be integrated into newborn screening for deafness.

genetics↗