Genome-wide DNA methylation profiling identifies ALDH1A3 promoter methylation as a prognostic predictor in G-CIMP− primary glioblastoma

To date, the aberrations in the DNA methylation patterns that are associated with different prognoses of G-CIMP− primary GBMs remain to be elucidated. Here, DNA methylation profiling of primary GBM tissues from 13 long-term survivors (LTS; overall survival ?18 months) and 20 short-term survivors (STS; overall survival ?9 months) was performed. Then G-CIMP+ samples were excluded. The differentially expressed CpG loci were identified between residual 18 STS and 9 LTS G-CIMP− samples. Methylation levels of 11 CpG loci (10 genes) were statistically significantly lower, and 43 CpG loci (40 genes) were statistically significantly higher in the tumor tissues of LTS than those of STS G-CIMP− samples (P < 0.01). Of the 43 CpG loci that were hypermethylated in LTS G-CIMP− samples, 3 CpG loci localized in the promoter of ALDH1A3. Furthermore, using an independent validation cohort containing 37 primary GBM samples without IDH1 mutation and MGMT promoter methylation, the hypermethylation status of ALDH1A3 promoter predicted a better prognosis with an accompanied low expression of ALDH1A3 protein. Taken together, our results defined prognosis-related methylation signatures systematically for the first time in G-CIMP− primary GBMs. ALDH1A3 promoter methylation conferred a favorable prognosis in G-CIMP− primary GBMs.     

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????Salivary gland tumor is one of the most common tumors in head and neck region with a great variety of morphology and biological behavior. Surgical operation is the major choice of salivary gland tumors. However?? except the benign and low-grade malignant tumors?? most salivary malignancies are in lack of specific treatment and the recurrent and metastic frequency is pretty high. Epigenetic study has become a hot spot of cancer research in recent years and one of widely studied field is the DNA promoter methylation. Our current article intends to discuss the possible application of DNA promoter methylation in the development??treatment and prognosis of salivary gland tumors.     

Subnuclear partitioning of rRNA genes between the nucleolus and nucleoplasm reflects alternative epiallelic states

Eukaryotes can have thousands of 45S ribosomal RNA (rRNA) genes, many of which are silenced during development. Using fluorescence-activated sorting techniques, we show that active rRNA genes in Arabidopsis thaliana are present within sorted nucleoli, whereas silenced rRNA genes are excluded. DNA methyltransferase (met1), histone deacetylase (hda6), or chromatin assembly (caf1) mutants that disrupt silencing abrogate this nucleoplasmic–nucleolar partitioning. Bisulfite sequencing data indicate that active nucleolar rRNA genes are nearly completely demethylated at promoter CGs, whereas silenced genes are nearly fully methylated. Collectively, the data reveal that rRNA genes occupy distinct but changeable nuclear territories according to their epigenetic state.     

The role of epigenetic therapies in colorectal cancer

Although developments in the diagnosis and therapy of colorectal cancer (CRC) have been made in the last decade, much work remains to be done as it remains the second leading cause of cancer death. It is now well established that epigenetic events, together with genetic alterations, are key events in initiation and progression of CRC. Epigenetics refers to heritable alterations in gene expression that do not involve changes in the DNA sequence. These alterations include DNA methylation, histone alterations, chromatin remodelers, and noncoding RNAs. In CRC, aberrations in epigenome may also involve in the development of drug resistance to conventional drugs such as 5-fluorouracil, oxaliplatin, and irinotecan. Thus, it has been suggested that combined therapies with epigenetic agents may reverse drug resistance. In this regard, DNA methyltransferase inhibitors and histone deacetylase inhibitors have been extensively investigated in CRC. The aim of this review is to provide a brief overview of the preclinical data that represent a proof of principle for the employment of epigenetic agents in CRC with a focus on the advantages of combinatorial therapy over single-drug treatment. We will also critically discuss the results and limitations of initial clinical experiences of epigenetic-based therapy in CRC and summarize ongoing clinical trials. Nevertheless, since recent translational research suggest that epigenetic modulators play a key role in augmenting immunogenicity of the tumor microenvironment and in restoring immune recognition, we will also highlight the recent developments of combinations strategies of immunotherapies and epigenetic therapies in CRC, summarizing preclinical, and clinical data to signify this evolving and promising field for CRC treatment.     

DNA甲基化与男性不育关系的研究进展

在严重的精子缺乏患者中普遍存在异常的表观遗传变化,已经发现亚甲基四氢叶酸还原酶(MTHFR)、PAX8、NTF3、SFN、HRAS、JHM2DA等基因DNA甲基化改变与不育患者中异常的精液参数有关,这些基因通常是高甲基化的.甲基化和去甲基化的正确调控对个体正常发育至关重要,微小的DNA甲基化异常与许多疾病有关,包括男性不育.阐述男性生殖细胞中正常的DNA甲基化,并对已经发现的异常DNA甲基化和男性不育的关系进行综述,从中探究男性不育的某些遗传学病因.     

BHA和β-ME对表观修饰后的NIH/3T3细胞向神经方向诱导的实验研究

目的通过联合应用表观修饰药物5-氮-2'-脱氧胞苷(5-aza-2'-deoxycytidine,5-aza-dC)和曲古抑菌素A(TrichstatinA,TSA)对NIH/3T3细胞进行重编程,应用β-羟基酸(betahydroxyacid,BHA)和β-巯基乙醇(β-mercaptoethanol,β-ME)进一步诱导,以期表达与神经细胞密切相关的基因。方法应用流式细胞技术检测实验组(4.5μM5-aza-dC+0.35μMTSA+1mMβ-ME+200μMBHA作用后的NIH/3T3细胞)和对照组中NIH/3T3细胞的DNA甲基化水平。应用RT-PCR的方法检测Oct4,Sox2,c-Myc和Klf4的表达,免疫细胞化学染色检测巢蛋白(nestin)和神经丝轻链(neurofilamentlightchain,NF-L)的表达情况。结果实验组NIH/3T3细胞DNA甲基化水平较对照组明显降低,细胞均呈现出Oct4,Sox2,c-Myc和Klf4基因的阳性表达。经过BHA和β-ME诱导后,NIH/3T3细胞呈巢蛋白和神经丝轻链阳性。结论表观修饰后的细胞经诱导后可以呈现nestin和NF-L的阳性表达。