A systematic quantitative approach comprehensively defines domain-specific functional pathways linked to Schizosaccharomyces pombe heterochromatin regulation.

Heterochromatin plays a critical role in regulating gene expression and maintaining genome integrity. While structural and enzymatic components have been linked to heterochromatin establishment, a comprehensive view of the underlying pathways at diverse heterochromatin domains remains elusive. Here, we developed a systematic approach to identify factors involved in heterochromatin silencing at pericentromeres, subtelomeres, and the silent mating type locus in Schizosaccharomyces pombe. Using quantitative measures, iterative genetic screening, and domain-specific heterochromatin reporters, we identified 369 mutants with different degrees of reduced or enhanced silencing. As expected, mutations in the core heterochromatin machinery globally decreased silencing. However, most other mutants exhibited distinct qualitative and quantitative profiles that indicate domain-specific functions. For example, decreased mating type silencing was linked to mutations in heterochromatin maintenance genes, while compromised subtelomere silencing was associated with metabolic pathways. Furthermore, similar phenotypic profiles revealed shared functions for subunits within complexes. We also discovered that the uncharacterized protein Dhm2 plays a crucial role in maintaining constitutive and facultative heterochromatin, while its absence caused phenotypes akin to DNA replication-deficient mutants. Collectively, our systematic approach unveiled a landscape of domain-specific heterochromatin regulators controlling distinct states and identified Dhm2 as a previously unknown factor linked to heterochromatin inheritance and replication fidelity.

Role of the Gut Microbiome in Autism Spectrum Disorders.

Autism spectrum disorder (ASD) is a severe neurodevelopmental or neuropsychiatric disorder with elusive etiology and obscure pathophysiology. Cognitive inabilities, impaired communication, repetitive behavior pattern, and restricted social interaction and communication lead to a debilitating situation in autism. The pattern of co-occurrence of medical comorbidities is most intriguing in autism, compared to any other neurodevelopmental disorders. They have an elevated comorbidity burden among which most frequently are seizures, psychiatric illness, and gastrointestinal disorders. The gut microbiota is believed to play a pivotal role in human health and disease through involvement in physiological homoeostasis, immunological development, glutathione metabolism, amino acid metabolism, etc., which in a reasonable way explain the role of gut-brain axis in autism. Branded as a neurodevelopmental disorder with psychiatric impairment and often misclassified as a mental disorder, many experts in the field think that a therapeutic solution to autism is unlikely to emerge. As the pathophysiology is still elusive, taking into account of the various symptoms that are concurrent in autism is important. Gastrointestinal problems that are seen associated with most of the autism cases suggest that it is not just a psychiatric disorder as many claim but have a physiological base, and alleviating the gastrointestinal problems could help alleviating the symptoms by bringing out the much needed overall improvement in the affected victims. A gut disorder akin to Crohn's disease is, sometimes, reported in autistic children, an extremely painful gastrointestinal disease which is named as autistic enterocolitis. This disturbed situation hypothesized to be initiated by dysbiosis or microbial imbalance could in turn perturb the coordination of microbiota-gut-brain axis which is important in human mental health as goes the popular dictum: "fix your gut, fix your brain."