Cohesin complexes mediate sister-chromatid cohesion in dividing cells but may also contribute to gene regulation in postmitotic cells. How cohesin regulates gene expression is not known. Here we describe cohesin-binding sites in the human genome and show that most of these are associated with the CCCTC-binding factor (CTCF), a zinc-finger protein required for transcriptional insulation. CTCF is dispensable for cohesin loading onto DNA, but is needed to enrich cohesin at specific binding sites. Cohesin enables CTCF to insulate promoters from distant enhancers and controls transcription at the H19/IGF2 (insulin-like growth factor 2) locus. This role of cohesin seems to be independent of its role in cohesion. We propose that cohesin functions as a transcriptional insulator, and speculate that subtle deficiencies in this function contribute to 'cohesinopathies' such as Cornelia de Lange syndrome.

Long-range regulatory elements and higher-order chromatin structure coordinate the expression of multiple genes in cluster, and CTCF/cohesin-mediated chromatin insulator may be a key in this regulation. The human apolipoprotein (APO) A1/C3/A4/A5 gene region, whose alterations increase the risk of dyslipidemia and atherosclerosis, is partitioned at least by three CTCF-enriched sites and three cohesin protein RAD21-enriched sites (two overlap with the CTCF sites), resulting in the formation of two transcribed chromatin loops by interactions between insulators. The C3 enhancer and APOC3/A4/A5 promoters reside in the same loop, where the APOC3/A4 promoters are pointed towards the C3 enhancer, whereas the APOA1 promoter is present in the different loop. The depletion of either CTCF or RAD21 disrupts the chromatin loop structure, together with significant changes in the APO expression and the localization of transcription factor hepatocyte nuclear factor (HNF)-4a and transcriptionally active form of RNA polymerase II at the APO promoters. Thus, CTCF/ cohesin-mediated insulators maintain the chromatin loop formation and the localization of transcriptional apparatus at the promoters, suggesting an essential role of chromatin insulation in controlling the expression of clustered genes.

Background and study aims Foveolar-type adenoma is described as a very rare tumor that occurs in individuals without Helicobacter pylori (HP) infection and diagnosed as adenocarcinoma in the Japanese Classification of Gastric Carcinoma (JCGC). However, we have frequently encountered patients with foveolar-type adenoma that endoscopically resembles a hyperplastic polyp, suggesting that it has just been overlooked to date. Here, we analyzed clinicopathological characteristics of a special subtype of foveolar-type adenoma showing specific endoscopic findings. Patients and methods From a total of 212 patients with gastric cancer resected during a 22-month period, we enrolled 14 (6.6 %) diagnosed with foveolar-type adenoma (adenocarcinoma in JCGC). HP infection status was determined by eradication history, HP serum IgG antibody level, urea breath test, and endoscopic and histological findings. All lesions were observed using white-light endoscopy and narrow-band imaging with magnification endoscopy (NBIME). Endoscopically resected lesions were histologically examined. Results None of 14 patients had a current or past history of HP infection. All lesions were visualized on non-atrophic gastric mucosa as small reddish protrusions with fine granular surface, showing a raspberry-like appearance. NBIME showed papillary or gyrus-like microstructures with irregular capillary. Lesions were histologically diagnosed as foveolar-type adenoma showing MUC5AC-positive gastric mucin phenotype. Ki-67 was overexpressed (median labeling index 69.9 %, range 28.4 – 92.1 %), though all lesions were an intraepithelial tumor without stromal invasion. p53 over-staining was not seen in any. Conclusions Raspberry-like lesions on non-atrophic gastric mucosa in HP-uninfected individuals should be evaluated for the possibility of a special subtype of foveolar-type adenoma.

These results suggest that PPIs cause both oral and gut microbiota alterations.

No abstract

The most suitable conditions for detection of EE are a lower esophagus biopsy site and the presence of exudates in cases suspicious of eosinophilic esophagitis shown by endoscopy.

Butyric acid, a short-chain fatty acid and one of the main metabolites of intestinal microbial fermentation of dietary fiber, has been shown to have an important role in maintaining the integrity of the intestinal mucosa, while it also has been shown to exert potent anti-inflammatory effects both in vitro and in vivo. However, the precise mechanisms underlying those effects have not been fully identified. We exposed colonic epithelial cells to butyric acid, then extracted total RNA samples, and subsequently hybridized them to microarray chips. Among the upregulated genes, milk fat globuleepidermal growth factor 8 (MFG-E8) was elevated by approximately fivefold. We previously reported that the potential therapeutic benefits of MFG-E8 in intestinal tissue injury were dependent not only on enhanced clearance of apoptotic cells but also required diverse cellular events for maintaining epithelial integrity. The influence of butyric acid on cell function is often attributed to its inhibition of histone deacetylases (HDACs). We found that acetylation on histone 3 lysine 9 (acetyl-H3K9) around the MFG-E8 promoter was significantly increased with butyric acid exposure. Experimental colitis was induced by administration of dextran sodium sulfate (DSS) in C57BL/6N (MFG-E8 þ / þ ) and MFG-E8 À / À mice. Although the colonic bacterial compositions in wild-type (WT) and MFG-E8 À / À mice were not significantly different, intrarectal administration of butyric acid during an acute phase of colitis attenuated intestinal inflammatory parameters and inhibited body weight loss in the WT mice. Our novel findings suggest that butyric acid has significant antiinflammatory effects partly via MFG-E8 on DSS-induced murine experimental colitis.

Objective Based on both endoscopic findings and serum auto-antibody levels, we determined the prevalence of autoimmune gastritis (AIG), which has not been previously reported, in individuals who underwent health checkup examinations in Japan. Methods At total of 6,739 subjects (4,288 males, 2,451 females; mean age 52.1 years) underwent an upper gastrointestinal endoscopic examination as part of an annual medical checkup. Those suspected to have AIG based on endoscopic evidence of proximal-predominant gastric mucosal atrophy were further examined for the presence of anti-parietal cells and anti-intrinsic factor antibodies, with a final diagnosis of AIG made in cases found to be positive for either or both of those factors. Results Of the 6,739 examined subjects, 46 were suspected to have AIG based on the endoscopic findings, of whom 33 were finally diagnosed with AIG, for an overall prevalence 0.49% (females 0.65%, males 0.40%). Seven with AIG also had thyroid disease, including Hashimoto's and Basedow disease, while none with AIG showed anemia in blood test findings. The prevalence of AIG was not different regardless of the H. pylori infection status (negative, positive, post-eradicated). Conclusion In individuals who underwent an upper gastrointestinal endoscopic examination as part of an annual checkup in Japan, the prevalence of AIG was 0.49%. We concluded that it is not uncommon for asymptomatic and healthy individuals to have AIG, and propose that additional studies are needed to clarify its prevalence as well as to establish the criteria used for diagnosis.