Male and female meiosis evince differential patterns in chiasma formation: a case study of ornamental plant, Delphinium ajacis L.

Chromosomal behaviour during megasporogenesis and microsporogenesis has been studied in ornamental Delphinium ajacis L. Meiosis in female sex cell initiates later than male. The floral buds which carry egg mother cell (EMC) at diplotene stage has pollen mother cells (PMCs) at tetrad stage of meiosis suggesting protandry. Although the 16 chromosomes formed regular eight bivalents in both the sex cells, they differed in overall chiasma frequency which was 32.95% higher in EMCs and found to be 18.52 ± 2.12 per cell. In PMCs, the average chiasma frequency recorded was 13.93 ± 1.40 per cell. Interestingly, this variation in chiasma frequency was largely confined to the two large bivalents which shared 42.61% chiasma per EMC. The use of Q–Q plot, Box plot and Whisker plot showed departure in the chiasma frequency distributions in EMCs and PMCs from the normal distribution pattern. The difference in chiasma frequency in the two sex cells was significant at all levels as indicated by the low P values of 3.094 9 10-11 obtained from nonparametric test, i.e. Wilcoxon rank-sum test. It is suggested that the two different mechanisms of recombination are operational in the two sex cells, and the sex differences of chiasma frequency could have arisen due to differential epigenetic modifications of the chromatin which pattern the double-strand breaks, and the position and frequency of crossing over visible as chiasmata.

Role of genomic imprinting in mammalian development

In mammals, DNA methyltransferases transfer a methyl group from S-adenosylmethionine to the 5 position ofcytosine in DNA. The product of this reaction, 5-methylcytosine (5mC), has many roles, particularly insuppressing transposable and repeat elements in DNA. Moreover, in many cellular systems, cell lineagespecification is accompanied by DNA demethylation at the promoters of genes expressed at high levels in thedifferentiated cells. However, since direct cleavage of the C-C bond connecting the methyl group to the 5position of cytosine is thermodynamically disfavoured, the question of whether DNA methylation wasreversible remained unclear for many decades. This puzzle was solved by our discovery of the TET (TenEleven Translocation) family of 5-methylcytosine oxidases, which use reduced iron, molecular oxygen and thetricarboxylic acid cycle metabolite 2-oxoglutarate (also known as a-ketoglutarate) to oxidise the methyl groupof 5mC to 5-hydroxymethylcytosine (5hmC) and beyond. TET-generated oxidised methylcytosines areintermediates in at least two pathways of DNA demethylation, which differ in their dependence on DNAreplication. In the decade since their discovery, TET enzymes have been shown to have important roles inembryonic development, cell lineage specification, neuronal function and cancer. We review these findings anddiscuss their implications here.

A Review of Epigenetic Modifications Regulate MicroRNA Expression in Lung Cancer / 中国肺癌杂志

Lung cancer is one of the primary causes of cancer-induced death among the world. Although the network of molecular implicated in lung cancer is gradually revealed, the exact molecular mechanism of its occurrence and development has not been fully elucidated. As a class of small and endogenous single-stranded non-coding RNAs, microRNAs (miRNAs) are found in a wide range of organisms from plants, viruses to humans. miRNAs involve various functions in normal lung tissue development. They take part in a large amount of biological processes including cell growth, metabolism, proliferation and differentiation. However, aberrant expression of miRNAs could induce the occurrence, development, invasion and metastasis of lung tumor, so it is deemed the novel biomarkers. Similar to that of protein-coding genes, expression and function of miRNA are regulated by various factors and the epigenetic network which includes DNA methylation and histone modification. Moreover, key enzymes driving epigenetic modifications are regulated by miRNAs. Therefore, better understanding of inextricable linkage between miRNAs and epigenome will provides a basis for the feasibility of miRNA-orientated diagnostic, therapeutic and prognostic strategies related to lung cancer in future.

Más allá de las moléculas Lo que los clínicos desconocen: acortando brechas / Filling the gap: Beyond molecules What clinicians ignore

Para acortar la brecha entre lo molecular y la clínica, el personal de atención médica debe tener un conocimiento básico de los mecanismos moleculares que gobiernan la identidad celular, mediante la activación selectiva de genes. La expresión diferencial de genes permite a las células sintetizar las proteínas requeridas para cumplir con sus funciones biológicas, y ello posibilita a las células responder a estímulos internos y externos. Para esto se debe tener primero acceso a los genes que codifican las proteínas, determinando el fenotipo celular. Modificaciones en la estructura de la cromatina permiten a la maquinaria transcripcional tener acceso a secuencias de ADN. El ADN es transcripto en ARNm, que sufre diversas modificaciones antes de salir del núcleo para ser traducido en una proteína en el citoplasma. Cualquier desregulación en alguno de los procesos asociados se presenta como una patología. A inicios del siglo XXI se reportó la secuenciación del genoma humano, y sorprendentemente uno de los principales hallazgos fue que solo un 2% de la secuencia codifica para proteínas, lo cual dejó un interrogante sobre cómo funcionan y se regulan los procesos genéticos que llevan a la identidad celular. Desde entonces las investigaciones han permitido utilizar los principios que rigen estos procesos para ampliar el conocimiento de los mecanismos asociados a enfermedades. Gracias a estos avances, se ha buscado determinar aplicaciones clínicas dirigidas a los procesos involucrados en la expresión génica diferencial, lograr una mejor comprensión sobre los procesos patológicos de la enfermedad y desarrollar herramientas diagnósticas.

To narrow the gap between the bench and the clinic, healthcare personnel should have a basic understanding of molecular mechanisms ruling cell identity, since it establishes the key differences between health and disease states. Differential gene expression allows for protein synthesis required for the cell's biological function. In this process genes are selected from the entire genome to meet the cell's biological functioning and respond to internal and external stimuli. To this end, first the chromatin must be remodeled for the transcriptional machinery to gain access to DNA sequences coding for particular genes. DNA can then be transcribed into mRNA, followed by different processes leading to mature mRNA leaving the nucleus for protein synthesis in the cytoplasm. Any dysregulation in these processes results in disease. In the beginning of this millennium the human genome project sequenced the whole genome. Surprisingly, one of the main findings was only 2% of the genome represented protein coding sequences, which raised the question about the remainder of the genome and cell identity. Based on principles derived from the human genome project many investigations have shed light on mechanisms associated with disease. Thanks to advancements in differential gene expression, researchers are seeking for a better understanding in pathological processes associated with disease and the development of diagnostic tools.

Research progress on epigenetic regulation-based mechanistic studies of Chinese herbal medicines in treatment of rheumatoid arthritis / 中国药理学通报

Epigenetic modifications represent an important mechanism underlying regulation of gene expression that enables human body to adapt to the changing environment. Research methods of epigenetic modifications are a frontier area for the study of molecular mechanisms underlying the pathogenesis of autoimmune diseases. Rheumatoid arthritis ( RA) has been one of the difficulties in both clinical and basic-research fields of autoimmune diseases. Hie etiology of RA remains elusive, and its pathogenesis involves complex immune and inflammatory pathways. Clinically ideal therapeutic approaches are still lacking for treatment of RA. Recent studies have shown that Chinese herbal medicine and bioactive components there of potentially target ep-igenetic modifications in the treatment of RA. In order to provide new research ideas for therapeutic interventions and mechanistic studies of RA, we here reviewed and summarized literature on the epigenetic mechanism underlying the generation and development of RA and therapeutic effects of Chinese herbal medicine in RA that involve targeting epigenetic modifications.

Comparison of the phenolic contents and epigenetic and genetic variability of wild and cultivated watercress (Rorippa nasturtium var. aquaticum L.)

Background: Epigenetic modifications are key factors modulating the expression of genes involved in the synthesis of phytochemicals. The knowledge of plant epigenetic and genetic variations can contribute to enhance the production of bioactive compounds. These issues have been little explored thus far in Rorippa nasturtium var. aquaticum L. (watercress), an edible and medicinal plant. The aim of the current study was to determine and compare the phenolic composition and epigenetic and genetic variations between wild and cultivated watercress. Results: Significant differences were found in the quantitative phenolic composition between wild and cultivated watercress. The eight primer combinations used in the methylation-sensitive amplification polymorphism (MSAP) method revealed different epigenetic status for each watercress type, the cultivated one being the most epigenetically variable. The genetic variability revealed by the EcoRI/MspI amplification profile and also by eight inter-simple sequence repeat (ISSR) primers was different between the two types of watercress. The results of the Mantel test showed that the correlation between genetic and epigenetic variations has diminished in the cultivated type. Cluster analyses showed that the epigenetic and genetic characterizations clearly discriminated between wild and cultivated watercress. Conclusions: Relevant chemical, epigenetic, and genetic differences have emerged between wild and cultivated watercress. These differences can contribute to fingerprint and develop quality control tools for the integral and safety use and the commercialization of watercress. The richness of epialleles could support the development of tools to manipulate the watercress epigenome to develop high bioproduct­producing cultivars

The alterations of PGC-1α expression and epigenetic modifications in the retina of streptozotocin-induced diabetic rats / 中华实验眼科杂志

Objective To investigate the role of epigenetic regulations of peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) in the development of diabetic retinopathy and the metabolic memory phenomenon after hyperglycemia was terminated.Methods Diabetic rat model was established by intraperitoneal injection of streptozotocin (STZ).Sixty diabetic rats were randomly divided into 3 groups,poor glycemic control group rats were maintained in poor glycemic control for 4 months;semi glycemic control group rats were maintained in poor glycemic control for 2 months,followed by good glycemic control for 2 additional months;good glycemic control group rats were maintained in good glycemic control for 4 months.Twenty normal rats served as control group.The mRNA expression of PGC-1α and superoxide dismutase 2 (SOD2) of retina were measured by real-time PCR;the expression of PGC-1α and manganese superoxide dismutase (MnSOD) protein were measured by Western blot;the situation of DNA methylation in the promotor region of PPARGC1A was measured by bisulfite sequencing.Results The body-weight in the control group was significantly higher than that in the poor glycemic control group,semi glycemic control group and good glycemic control group (all at P =0.000).The blood glucose value in the poor glycemic control group was significantly higher than that in the control group (P =0.000).The expression levels of PGC-1 α mRNA were significantly lower and the expression levels of SOD2 mRNA were significantly higher in the good glycemic control group,semi glycemic control group and poor glycemic control group than those in the control group (all at P＜0.05).The expression levels of PGC-1α and SOD2 mRNA were significantly different between the good glycemic control group and poor glycemic control group (both at P＜0.05).Compared with the control group,the expression levels of PGC-1α and MnSOD protein were decreased in the diabetic model groups,with significant differences between them (all at P＜0.05).The expression level of PGC-1 α protein was significantly higher in the good glycemic control group than that in the poor glycemic control group (P＜0.05).Diabetes increased DNA methylation in the promotor region of PPARGC1A gene of retina.The DNA methylation level was significantly higher in the poor glycemic control group and semi glycemic control group than that in the control group (P =0.008,0.031).No statistical difference was found between the poor glycemic control group and semi glycemic control group (P ＞ 0.05).Conclusions The expressions of PGC-1o mRNA and protein and MnSOD protein in the retina of STZ induced diabetic rats are decreased,the expression of SOD2 mRNA is increased,the expression changes have metabolic memory characteristics.Increased DNA methylation in the promotor region of PPARGC1A when exposed to high glucose may have a role in the regulation of PGC-1 α expression and metabolic memory.

Research progress on regulation mechanism of epigenetic modifications for drug transporters / 药物评价研究

Drug transporters play a key role in drug absorption,distribution and excretion.The distribution and expression of transporters in tissues and organs are regulated by epigenetic modifications,resulting in individual differences of drugs disposition significantly.With the development of epigenetics,researches on the regulation of drug transporters expression based on epigenetic modifications (DNA methylation,histone modification,microRNA interference,etc.) have been more and more reported.In this paper,we will summarize the epigenetic modifications regulating drug transporters.