Polycomb Group Proteins (PcG) are a family of epigenetic regulators responsible for the repression of an array of genes important in development and cell fate specification. PcG proteins complex to form two types of epigenetic regulators: Polycomb Repressive Complex 1 and 2 (PRC1 and PRC2). Although the mechanisms regulating PRC2 recruitment and activity in mammals remain poorly understood, recent work has identified a non-canonical PRC2 in mouse embryonic stem cells (mESC) with unique activities required for repression of PRC2 target genes and necessary for mESC differentiation and somatic cell reprogramming. Here we review the functions of PRC2 in embryonic stem cells and explore the role of the newly identified mESC specific PRC2 regulatory subunits Jarid2 (jumonji, AT rich interactive domain 2), Mtf2 (metal response element binding transcription factor 2) and esPRC2p48.
Animals ; Cell Differentiation ; genetics ; Embryonic Stem Cells ; cytology ; metabolism ; Epigenesis, Genetic ; Gene Expression Regulation, Developmental ; Histones ; genetics ; metabolism ; Mice ; Nerve Tissue Proteins ; genetics ; metabolism ; Polycomb Repressive Complex 2 ; Polycomb-Group Proteins ; Protein Binding ; genetics ; Protein Subunits ; genetics ; metabolism ; Repressor Proteins ; genetics ; metabolism

Background: The contributions of the gut microbiota to obesity and metabolic disease represent a potentially modifiable factor that may explain variation in risk between individuals. This study aimed to explore relationships among microbial composition and imputed functional attributes, a range of soluble metabolic and immune indices, and gene expression markers in males with or without evidence of metabolic dysregulation (MetDys). Methods: This case-control study included healthy males (n=15; 41.9±11.7 years; body mass index [BMI], 22.9±1.2 kg/m2 ) and males with evidence of MetDys (n= 14; 46.6±10.0 years; BMI, 35.1±3.3 kg/m2 ) who provided blood and faecal samples for assessment of a range of metabolic and immune markers and microbial composition using 16S rRNA gene sequencing. Metagenomic functions were imputed from microbial sequence data for analysis. Results: In addition to elevated values in a range of traditional metabolic, adipokine and inflammatory indices in the MetDys group, 23 immunomodulatory genes were significantly altered in the MetDys group. Overall microbial diversity did not differ between groups; however, a trend for a higher relative abundance of the Bacteroidetes (P=0.06) and a lower relative abundance of the Verrucomicrobia (P=0.09) phyla was noted in the MetDys group. Using both family- and genera-level classifications, a partial least square discriminant analysis revealed unique microbial signatures between the groups. Conclusion These findings confirm the need for ongoing investigations in human clinical cohorts to further resolve the relationships between the gut microbiota and metabolic and immune markers and risk for metabolic disease.

Background: The contributions of the gut microbiota to obesity and metabolic disease represent a potentially modifiable factor that may explain variation in risk between individuals. This study aimed to explore relationships among microbial composition and imputed functional attributes, a range of soluble metabolic and immune indices, and gene expression markers in males with or without evidence of metabolic dysregulation (MetDys). Methods: This case-control study included healthy males (n=15; 41.9±11.7 years; body mass index [BMI], 22.9±1.2 kg/m2 ) and males with evidence of MetDys (n= 14; 46.6±10.0 years; BMI, 35.1±3.3 kg/m2 ) who provided blood and faecal samples for assessment of a range of metabolic and immune markers and microbial composition using 16S rRNA gene sequencing. Metagenomic functions were imputed from microbial sequence data for analysis. Results: In addition to elevated values in a range of traditional metabolic, adipokine and inflammatory indices in the MetDys group, 23 immunomodulatory genes were significantly altered in the MetDys group. Overall microbial diversity did not differ between groups; however, a trend for a higher relative abundance of the Bacteroidetes (P=0.06) and a lower relative abundance of the Verrucomicrobia (P=0.09) phyla was noted in the MetDys group. Using both family- and genera-level classifications, a partial least square discriminant analysis revealed unique microbial signatures between the groups. Conclusion These findings confirm the need for ongoing investigations in human clinical cohorts to further resolve the relationships between the gut microbiota and metabolic and immune markers and risk for metabolic disease.

Background: The contributions of the gut microbiota to obesity and metabolic disease represent a potentially modifiable factor that may explain variation in risk between individuals. This study aimed to explore relationships among microbial composition and imputed functional attributes, a range of soluble metabolic and immune indices, and gene expression markers in males with or without evidence of metabolic dysregulation (MetDys). Methods: This case-control study included healthy males (n=15; 41.9±11.7 years; body mass index [BMI], 22.9±1.2 kg/m2 ) and males with evidence of MetDys (n= 14; 46.6±10.0 years; BMI, 35.1±3.3 kg/m2 ) who provided blood and faecal samples for assessment of a range of metabolic and immune markers and microbial composition using 16S rRNA gene sequencing. Metagenomic functions were imputed from microbial sequence data for analysis. Results: In addition to elevated values in a range of traditional metabolic, adipokine and inflammatory indices in the MetDys group, 23 immunomodulatory genes were significantly altered in the MetDys group. Overall microbial diversity did not differ between groups; however, a trend for a higher relative abundance of the Bacteroidetes (P=0.06) and a lower relative abundance of the Verrucomicrobia (P=0.09) phyla was noted in the MetDys group. Using both family- and genera-level classifications, a partial least square discriminant analysis revealed unique microbial signatures between the groups. Conclusion These findings confirm the need for ongoing investigations in human clinical cohorts to further resolve the relationships between the gut microbiota and metabolic and immune markers and risk for metabolic disease.

There is evidence that a substantial part of genetic predisposition to prostate cancer (PCa) may be due to lower penetrance genes which are found by genome-wide association studies. We have recently conducted such a study and seven new regions of the genome linked to PCa risk have been identified. Three of these loci contain candidate susceptibility genes: MSMB, LMTK2 and KLK2/3. The MSMB and KLK2/3 genes may be useful for PCa screening, and the LMTK2 gene might provide a potential therapeutic target. Together with results from other groups, there are now 23 germline genetic variants which have been reported. These results have the potential to be developed into a genetic test. However, we consider that marketing of tests to the public is premature, as PCa risk can not be evaluated fully at this stage and the appropriate screening protocols need to be developed. Follow-up validation studies, as well as studies to explore the psychological implications of genetic profile testing, will be vital prior to roll out into healthcare.
Genetic Predisposition to Disease ; genetics ; Genetic Testing ; Humans ; Kallikreins ; genetics ; Male ; Membrane Proteins ; genetics ; Prostatic Neoplasms ; diagnosis ; genetics ; Prostatic Secretory Proteins ; genetics ; Protein-Serine-Threonine Kinases ; genetics ; Risk Factors