Fungi are able to switch between different lifestyles in order to adapt to environmental changes. Their ecological strategy is connected to their secretome as fungi obtain nutrients by secreting hydrolytic enzymes to their surrounding and acquiring the digested molecules. We focus on fungal serine proteases (SPs), the phylogenetic distribution of which is barely described so far. In order to collect a complete set of fungal proteases, we searched over 600 fungal proteomes. Obtained results suggest that serine proteases are more ubiquitous than expected. From 54 SP families described in MEROPS Peptidase Database, 21 are present in fungi. Interestingly, 14 of them are also present in Metazoa and Viridiplantae – this suggests that, except one (S64), all fungal SP families evolved before plants and fungi diverged. Most representatives of sequenced eukaryotic lineages encode a set of 13–16 SP families. The number of SPs from each family varies among the analysed taxa. The most abundant are S8 proteases. In order to verify hypotheses linking lifestyle and expansions of particular SP, we performed statistical analyses and revealed previously undescribed associations. Here, we present a comprehensive evolutionary history of fungal SP families in the context of fungal ecology and fungal tree of life.

Chromatin structure and accessibility, and combinatorial binding of transcription factors to regulatory elements in genomic DNA control transcription. Genetic variations in genes encoding histones, epigenetics-related enzymes or modifiers affect chromatin structure/dynamics and result in alterations in gene expression contributing to cancer development or progression. Gliomas are brain tumors frequently associated with epigenetics-related gene deregulation. We perform whole-genome mapping of chromatin accessibility, histone modifications, DNA methylation patterns and transcriptome analysis simultaneously in multiple tumor samples to unravel epigenetic dysfunctions driving gliomagenesis. Based on the results of the integrative analysis of the acquired profiles, we create an atlas of active enhancers and promoters in benign and malignant gliomas. We explore these elements and intersect with Hi-C data to uncover molecular mechanisms instructing gene expression in gliomas.

Observations from numerous clinical, epidemiological and serological studies link periodontitis with severity and progression of rheumatoid arthritis. The strong association is observed despite totally different aetiology of these two diseases, periodontitis being driven by dysbiotic microbial flora on the tooth surface below the gum line, while rheumatoid arthritis being the autoimmune disease powered by anti-citrullinated protein antibodies (ACPAs). Here we discuss genetic and environmental risk factors underlying development of both diseases with special emphasis on bacteria implicated in pathogenicity of periodontitis. Individual periodontal pathogens and their virulence factors are argued as potentially contributing to putative causative link between periodontal infection and initiation of a chain of events leading to breakdown of immunotolerance and development of ACPAs. In this respect peptidylarginine deiminase, an enzyme unique among prokaryotes for Porphyromonas gingivalis, is elaborated as a potential mechanistic link between this major periodontal pathogen and initiation of rheumatoid arthritis development.

Background Hereditary gingival fibromatosis (HGF) is a rare condition characterized by slowly progressive overgrowth of the gingiva. The severity of overgrowth may differ from mild causing phonetic and masticatory issues, to severe resulting in diastemas or malposition of teeth. Both, autosomal-dominant and autosomal-recessive forms of HGF are described. The aim of this review is a clinical overview, as well as a summary and discussion of the involvement of candidate chromosomal regions, pathogenic variants of genes, and candidate genes in the pathogenesis of HGF. The loci related to non-syndromic HGF have been identified on chromosome 2 (GINGF, GINGF3), chromosome 5 (GINGF2), chromosome 11 (GINGF4), and 4 (GINGF5). Of these loci, pathogenic variants of the SOS-1 and REST genes inducing HGF have been identified in the GINGF and the GINGF5, respectively. Furthermore, among the top 10 clusters of genes ranked by enrichment score, ATP binding, and fibronectin encoding genes were proposed as related to HGF. Conclusion The analysis of clinical reports as well as translational genetic studies published since the late’90s indicate the clinical and genetic heterogeneity of non-syndromic HGF and point out the importance of genetic studies and bioinformatics of more numerous unrelated families to identify novel pathogenic variants potentially inducing HGF. This strategy will help to unravel the molecular  mechanisms as well as uncover specific targets for novel and less invasive therapies of this rare, orphan condition.

Chromatin structure and accessibility, and combinatorial binding of transcription factors to regulatory elements in genomic DNA control transcription. Genetic variations in genes encoding histones, epigenetics-related enzymes or modifiers affect chromatin structure/dynamics and result in alterations in gene expression contributing to cancer development or progression. Gliomas are brain tumors frequently associated with epigenetics-related gene deregulation. We performed whole-genome mapping of chromatin accessibility, histone modifications, DNA methylation patterns and transcriptome analysis simultaneously in multiple tumor samples to unravel novel epigenetic dysfunctions driving gliomagenesis. Based on the results of the integrative analysis of the acquired profiles, we created an atlas of active enhancers and promoters in benign and malignant gliomas. We explored these elements and intersected with Hi-C data to uncover molecular SignificanceEpigenetics-driven deregulation of gene expression accompanies cancer development, but its comprehensive characterization in cancer patients is fragmentary. We performed wholegenome profiling of gene expression, open chromatin, histone modifications and DNAmethylation profiles in the same samples from benign and malignant gliomas. Our study provides a first comprehensive atlas of active regulatory elements in gliomas, which allowed identification of the functional enhancers and promoters in patient samples. This comprehensive approach revealed epigenetic patterns influencing gene expression in benign gliomas and a new pathogenic mechanism involving FOXM1-driven network in glioblastomas. This atlas provides a common set of elements for cross-comparisons of existing and new datasets, prompting novel discoveries and better understanding of gliomagenesis. Highlights We provide an atlas of cis-regulatory elements active in human gliomas  Enhancer-promoter contacts operating in gliomas are revealed  Diverse enhancer activation is pronounced in malignant gliomas  Chromatin loop activates FOXM1-ANXA2R pathological network in glioblastomas.

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