Oocyte growth is a key step in forming mature eggs that are ready to be fertilized. The states and modifications of chromatin represent critical sources of information for this process. However, the dynamics and interrelations of these chromatin characteristics remain elusive. In this study, we developed an improved scCOOL-seq technique (iscCOOL-seq), which is a multi-omics, single-cell and single-base resolution method with high mapping rates, and explored the chromatin accessibility landscape and its relationship to DNA methylation in growing mouse oocytes. The most dramatic change in chromatin accessibility occurs during oocyte growth initiation, accompanied with prominent transcriptome alterations and an elevated variation in DNA methylation levels among individual oocytes. Unlike CpG islands (CGIs), partially methylated domains (PMDs) are associated with a low density of nucleosome-depleted regions (NDRs) during the whole maturation period. Surprisingly, highly expressed genes are usually associated with NDRs at their transcriptional end sites (TESs). In addition, genes with de novo methylated gene bodies during oocyte maturation are already open at their promoters before oocyte growth initiation. Furthermore, epigenetic and transcription factors that might be involved in oocyte maturation are identified. Our work paves the way for dissecting the complex, yet highly coordinated, epigenetic alterations during mouse oocyte growth and the establishment of totipotency.

BackgroundGenome-wide association studies have identified that genetic variants in 8q24 confer susceptibility to colorectal cancer (CRC). Recently, a novel lncRNA (PRNCR1) that located in the 8q24 was discovered. Single nucleotide polymorphisms (SNPs) in the lncRNAs may influence the process of splicing and stability of mRNA conformation, resulting in the modification of its interacting partners. We hypothesized that SNPs in the lncRNA PRNCR1 may be related to the risk of CRC.MethodsWe conducted a case–control study and genotyped five tag SNPs in the lncRNA PRNCR1 in 908 subjects including 313 cases with CRC and 595 control subjects using polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP) assay.ResultsIn overall analyses, we found that the rs13252298 and rs1456315 were associated with significantly decreased risks of CRC. In stratification analyses, we found that CRC patients carrying the rs1456315G were likely to have a tumor size of greater than 5 cm (G vs. A: adjusted OR = 1.56, 95% CI: 1.10-2.23). Additionally, patients with the rs7007694C and rs16901946G had decreased risks to develop poorly differentiated CRC, whereas patients with the rs1456315G had an increased risk to develop poorly differentiated CRC.ConclusionThese findings suggest that SNPs in the lncRNA PRNCR1 may contribute to susceptibility to CRC.

BackgroundThe purpose of this study was to assess the expression levels for TβRI, TβRII, and TβRIII in epithelial layers of oral premalignant lesions (oral leukoplakia, OLK) and oral squamous cell carcinoma (OSCC), as well as in oral carcinoma-associated fibroblasts (CAFs), with the final goal of exploring the roles of various types of TβRs in carcinogenesis of oral mucosa.MethodsNormal oral tissues, OLK, and OSCC were obtained from 138 previously untreated patients. Seven primary human oral CAF lines and six primary normal fibroblast (NF) lines were established successfully via cell culture. The three receptors were detected using immunohistochemical (IHC), quantitative RT-PCR, and Western blot approaches.ResultsIHC signals for TβRII and TβRIII in the epithelial layer decreased in tissue samples with increasing disease aggressiveness (P < 0.05); no expression differences were observed for TβRI, in OLK and OSCC (P > 0.05); and TβRII and TβRIII were significantly downregulated in CAFs compared with NFs, at the mRNA and protein levels (P < 0.05). Exogenous expression of TGF-β1 led to a remarkable decrease in the expression of TβRII and TβRIII in CAFs (P < 0.05).ConclusionThis study provides the first evidence that the loss of TβRII and TβRIII expression in oral epithelium and stroma is a common event in OSCC. The restoration of the expression of TβRII and TβRIII in oral cancerous tissues may represent a novel strategy for the treatment of oral carcinoma.

J. Neurochem. (2011) 119, 644–653. Abstract Excessive astrogliosis is a major impediment to axonal regeneration in CNS disorders. Overcoming this inhibitory barrier of reactive astrocytes might be crucial for CNS repair. Up‐regulation and activation of epidermal growth factor receptor (EGFR) has been shown to trigger quiescent astrocytes into reactive astrocytes in response to several neural injuries. In this study, we investigated the effects of EGFR blockade in cultured astrocytes exposure to oxygen–glucose deprivation/reoxygenation (OGD/R) and in the rat middle cerebral artery occlusion (MCAO) model. Astrocytes in primary culture were used for OGD/R model and adult male Sprague–Dawley rats were used for MCAO model. Cell cycle progression of astrocytes in vitro was studied by flow cytometric analysis. Expression of phosphorylated epidermal growth factor receptor (p‐EGFR), glial fibrillary acidic protein (GFAP), and cell proliferation‐related molecules in vitro and in vivo were evaluated by immunostaining and western blot analysis. Neuronal apoptosis after MCAO was determined by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) method. Neurologic scores and infarct volumes post‐ischemia were assessed in the rat MCAO model. Astrocytes became activated in the cultured astrocytes exposure to OGD/R and in the rat brain after MCAO, accompanied with phosphorylation of EGFR. EGFR blockade significantly decreased expression of p‐EGFR, inhibited cell cycle progression of astrocytes, and reduced reactive astrogliosis in vitro and in vivo. EGFR inhibition also reduced infarct volumes and improved neurologic scores of rats after MCAO. Our findings indicated that blocking EGFR pathway might attenuate reactive astrogliosis through inhibiting cell cycle progression and protect against ischemic brain injury in rats.