Project description:To reveal the role of sulfur metabolism genes in memory formation processes, transcriptome libraries were obtained from the heads of 5-day-old naive males. The libraries were generated from Drosophila strains created in our laboratory with deleted cbs genes ( CBS-/-(5) and CBS-/-(8), cse (CSE-/-) and strains with double deletion of cbs and cse genes (CBS-/-,CSE-/-(1) and (CBS-/-,CSE-/-(2). Strain 58492, in which deletions were introduced by the CRISP/CAS9 method, was used as a control strain.

2022-04-14 | GSE200397 | GEO

Highly recurrent CBS epimutations in gastric cancer CpG island methylator phenotypes and inflammation

Project description:CIMP (CpG island methylator phenotype) is an epigenetic molecular subtype, observed in multiple malignancies and associated with the epigenetic silencing of tumour suppressors. Currently, for most cancers including gastric cancer [GC], mechanisms underlying CIMP remain poorly understood. We sought to discover molecular contributors to CIMP in GC, by performing global DNA methylation, gene expression, and proteomics profiling across 14 gastric cell lines, followed by similar integrative analysis in 50 GC cell lines and 467 primary GCs. We identify the cystathionine beta-synthase enzyme (CBS) as a highly recurrent target of epigenetic silencing in CIMP GC. Likewise, we show that CBS epimutations are significantly associated with CIMP in various other cancers, occurring even in premalignant gastroesophageal conditions and longitudinally linked to clinical persistence. Of note, CRISPR deletion of CBS in normal gastric epithelial cells induces widespread DNA methylation changes that overlap with primary GC CIMP patterns. Reflecting its metabolic role as a gatekeeper interlinking the methionine and homocysteine cycles, CBS loss in vitro also causes reductions in the anti-inflammatory gasotransmitter hydrogen sulphide (H2S), with concomitant increase in NF-κB activity. In a murine genetic model of CBS-deficiency, preliminary data indicate upregulated immune-mediated transcriptional signatures in the stomach. Our results implicate CBS as a bi-faceted modifier of aberrant DNA methylation and inflammation in GC and highlights H2S donors as a potential new therapy for CBS-silenced lesions.

2021-04-19 | GSE149411 | GEO

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