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Chinese hamster ovary (CHO) cells play an irreplaceable role in biopharmaceuticals because the cells can be adapted to grow in suspension cultures and are capable of producing high quality biologics exhibiting human-like post-translational modifications. However, gene expression regulation such as transgene silencing and epigenetic modifications may reduce the recombinant protein production due to the decrease of expression stability of CHO cells. This paper summarized the role of epigenetic modifications in CHO cells, including DNA methylation, histone modification and miRNA, as well as their effects on gene expression regulation.

Lung cancer is becoming an increasing threat to Chinese residents and its incidence continues to rise while the treatment effect is far from satisfactory. Hence, it is essential to improve the level of early diagnosis, treatment, prognosis in lung cancer. An epigenetic trait is a stably heritable phenotype resulting from changes in a chromosome without alterations in the DNA sequence. The epigenetic studies, such as DNA methylation and histone methylation, are progressing rapidly in oncology research. A comprehensive understanding of its development status and existing problems is of great significance for the future research and the implementation of precision medicine. Herein, we aim to outline the progress of DNA methylation and histone methylation modification in lung cancer and make a prospect for the future research.

Heart is the first organ to function during mammalian embryogenesis. The differentiation of embryonic stem cells (ESCs) into cardiomyocyte is complex and dynamic, which involves 4 differentiation stages including ESCs, mesoderm, cardiac precursor, and terminal cardiomyocytes. Abnormal expression of certain genes can lead to congenital heart diseases during cardiomyocyte differentiation. Epigenetic regulation plays a crucial role on the switch of gene activation and deactivation during cardiomyocyte differentiation. Non-coding RNA, particularly microRNA and long non-coding RNA, may significantly influence gene expression. Exploring the regulatory roles of non-coding RNA in cardiomyocyte differentiation may contribute to the understanding of the functions of myocardial cells and mechanism of congenital heart diseases.

The occurrence and development of acute myeloid leukemia (AML) is not only related to gene mutations, but also influenced by abnormal epigenetic regulation, in which DNA methylation is one of the most important mechanisms. Abnormal DNA methylation may lead to the activation of oncogene and the inactivation of tumor suppressor gene, resulting in the occurrence of leukemia. The mutations of DNA methylation enzymes associated with AML may have certain characteristics. The AML with recurrent cytogenetic abnormalities is also related to abnormal methylation. Some fusion genes can alter DNA methylation status to participate in the pathogenesis of leukemia. In addition, chemotherapy drug resistance in patients with AML is associated with the change of gene methylation status. Considering the reversibility of the epigenetic modification, targeted methylation therapy has become a hotspot of AML research.

Advances in genomics and molecular biology have led to discovery of a large group of previous uncharacterized long non-noncoding RNAs (lncRNAs). Whether all of these transcripts are functional remains to be elucidated, but emerging evidence indicates that many lncRNAs play roles in multiple biological processes and that dysregulation of lncRNAs is often associated with diseases. Of significant interest, recent studies suggest that almost all of the regulatory lncRNAs function through interacting with different biological macromolecules such as DNA, RNA, and protein. In this review, we summarize the mechanisms by which lncRNAs regulate gene expression at epigenetic, transcriptional and post-transcriptional levels, and discuss the role of lncRNAs in tumorigenesis and host defense. Distinct from small ncRNAs that regulate gene expression mainly through base pairing to target transcripts, most identified lncRNAs function by regu-lating protein activity or maintaining the integrity of protein complexes. As a result, identification and characterization of the lncRNA-protein interactions may be the primary task to decode functional lncRNAs.

Cancer is a leading cause of death worldwide and the total number of cases globally keeps increasing. For many years, cancer has been thought to be caused by a series of DNA sequence alterations and thus is thought to be a "genetic" disease. However, studies in the last decade, including the large-scale cancer genomics projects, have highlighted the rising importance of epigenetic regulation in cancer. Here, we review recent advances in understanding how chromatin-based epigenetic regulation participates in tumorigenesis and discuss the growing implications of these advances for developing novel strategies to prevent, diagnose, as well as treat cancer.

Recently, 5-hydroxymethyl cytosine (5-hmC) has been discovered as a naturally existed component of normal mammalian genomic DNAs, and it is generally accepted as the sixth base in the genome. This review will introduce the recent advances in the researches on 5-hmC of its formation, tissue-specific distribution, the roles in cell differentiation and gene expression regulation, and the connections as a epigenetic marker with diseases, such as various cancers. We also summarized the current development of the methodologies to detect methylated or hydroxymetholated cytosines of cells at the genomic levels.

It has been demonstrated that the social environment early in life has a long lasting effect on the physical and psychological health of the human body. However, understanding of the relationship between early life experiences, such as maternal care behavior, and life-long cognitive and emotional health can only rely on the studies on animal models. In this paper, we summarized the maternal care effects on both defensive responses to stress and reproductive behavior in rat, and explored the possible underlying epigenetic mechanisms for these effects. Based on this model, we further investigated the significance of such epigenetic effects on human mental health.

Histone modification is an important component of epigenetic regulation, which can regulate eukaryotic gene expression by changing the structure of chromatin and interacting with other regulatory proteins. Abnormal histone modifications may lead to a variety of diseases, while the reversibility of histone modification provides a new way of thinking for treatment of these diseases. In this paper, we discussed the mechanism of histone lysine methylation related to congenital heart defect in order to provide a useful reference for researchers working in this area.

Inflammation is controlled by genetic and non-genetic factors (environment and epigenetics), within non-genetic factors, epigenetics play important roles in the development of inflammation. Epigenetic modifications, referring to changes in phenotype or gene expression caused by mechanisms other than changes in the underlying DNA sequence, mainly include DNA methylation and histone modification. Epigenetic study builds up the relationships between microorganism and inflammation. In inflammation responses, differentiation of T helper cells and gene expression of cytokine and chemokine are all regulated by epigenetics. Here, we reviewed the regulation mechanisms of DNA methylation and histone modifications on inflammation, especially on cow mastitis. The progress and application trends of epigenetics on treatment of mastitis and breeding for mastitis resistance in dairy cattle are also discussed.

Intracytoplasmic sperm injection (ICSI) can be applied to treat male infertility patients of oligospermia, asthenospermia, teratospermia, azoospermia and failure of the common in-vitro fertilization (IVF), which may overcome the sperm deficiency and even obtain sperms directly from percutaneous epididymal sperm aspiration (PESA) and testicular sperm extraction (TESE). As for direct injection of a single sperm into an egg, the ICSI disobeys the biological laws of natural insemination, thus leading to high genetic and epigenetic risk for patients owing to genetic and epigenetic defect of sperm. By reviewing the genetic and epigenetic defects of ICSI sperm, as well as related diseases, this article aims at understanding of the risks resulting from the genetic and epigenetic defects of ICSI sperm at a molecular mechanism level. The results show that the quality control of ICSI sperm via detecting its epigenetic factors, such as methylated DNA and acetylated histone, is essential for reducing the genetic and epigenetic risk from ICSI.

Both hitone modification and DNA methylation remodulate chromatin structure and control gene expression or silence. As a main enzyme for DNA methylation, DNA methyltransferase (Dnmt) is not only associated with DNA methylation, but also links to many important biological activities, including cell proliferation, senescence and cancer development. This review focuses on structure, regulation and function in biological processes of Dnmt.

Epigenetics is the study of meiotically and mitotically heritable changes in gene expression that are not coded for in the underlying DNA sequence. The term epigenetics is derived from epi- (meaning upon) and genetics. Epigenetic regulation of mammalian gene expression has profound effects in controlling cell growth, differentiation and cancer development. The important epigenetic mechanisms include DNA cytosine methylation, histone modifications and the more recently discovered non-coding RNAs. Non-coding RNAs are functional RNA molecules that are not translated into proteins. The main classes of regulatory non-coding RNAs include siRNA, miRNA, piRNA and long non-coding RNAs. There is growing evidence that regulatory non-coding RNAs play essential roles in the regulation of gene expression and are impor-tant in mammalian development and disease processes. Here, we review current research efforts aimed at understanding non-coding RNAs and their mechanisms of function in mammalian cells.

Epigenetic modifications, including DNA methylation, histone modifications, RNA epigenetics and nucleosome remodeling, are important for gene transcription, but such modifications do not change the coding sequence of the gene. Although these events are heritable, they are potentially reversible, thus opening up opportunities for the therapy of cancer. So epigenetic modifications have been thrusted into the forefront of new drug discoveries. Current knowledge suggests that the agents that intervene epigenetics by "turning back on" silenced genes may represent a significant advancement in treating many forms of cancer. In this review, we summarized the research progress of epigenetic gene regulation and the proteins which could read epigenetic codes. And the relationship between epigenetics and cancer was discussed comprehensively.

To discuss the effect of co-culture on the quality of mouse blastocysts and their epigenetic modification. We divided mouse zygotes into three co-culture experiment groups : with granular cells (group I ), oviduct epithelium cells (group II) and oviduct tissue (group III). Meanwhile, we set up control A (cultured in vitro, only KSOM (KCl+ simplex optimized medium)) and control B (cultured in vivo). Then we compared cleavage rate and blastocyst rate among different groups. After that we evaluated the quality of blastocysts by using ICM/TE (Inner cell mass/Trophectoderm cells) ratio via staining with propidium iodide and Hoechest333258, and analyzed the level of genome methylation and histone acetylation by immunofluorescence. Compared with the control group A, the co-culture groups had increased cleavage rate and blastocyst rate (P < 0.05), blastocyst cells and the ICM/TE ratio of co-culture groups were higher (P < 0.05), the level of genome methylation and histone acetylation had no significant difference between groups in vitro (P > 0.05), but the level of genome methylation in vivo was significantly higher than that of in vitro (P < 0.05). The co-culture methods can successfully promote the development rate of embryos in vitro, and improve the quality of the blastocyst. However, the methods have drawbacks in changing the abnormal genome methylation with in vitro culture.

DNA methylation is one of the major epigenetic modifications. It is very important to the regulation of gene expression. In present study, an autoploidy series (2x, 3x and 4x) in watermelon (Citrullus lanatus) was constructed and MSAP (Methylation-Sensitive Amplification Polymorphism) analysis was conducted to elucidate the level and pattern of DNA methylation at CCGG sites in different ploidy watermelons. Totally, 1883 genetic loci were produced by 23 pairs of selective primers, of which 647, 655 and 581 sites were detected in diploid, autotriploid and autotetraploid, respectively. The methylation sites were 181, 150 and 159, and the corresponding total methylation ratios were 28.0%, 22.9% and 27.4% in 2x, 3x and 4x, respectively, of which the fully methylation sites were 121, 80 and 82, and the corresponding fully methylation ratios were 18.7%, 12.2% and 14.1%. Further analysis of the pattern of DNA methylation suggested that compared 4x with 2x, about half of detected sites (54.4%) shown changes of DNA methylation patterns. Similarly, compared 4x with 3x, 45.4% sites also shown changes of DNA methylation patterns. Moreover, the trend of DNA methylation adjustment mainly involved increase of DNA methylation levels in 4x. However, compared 3x with 2x or 4x, although the changes of DNA methylation pattern also widely occurred, which involved 41.6% (compared 3x with 2x) and 45.4% (compared 3x with 4x) sites, respectively, the trend of DNA methylation adjustment mainly involved decrease of DNA methylation levels in 3x. All these results indicated that DNA methylation events were widely existed in different ploidy watermelons. However, not only based on the total DNA methylation ratio or fully DNA methylation ratio, the results both implied that the DNA methylation levels were not closely associated with the autopolyploidy level in watermelon. Autotriploid watermelon shows obvious low level of DNA methylation. Analysis of DNA methylation patterns also suggested that the adjustment of DNA methylation patterns in autotriploid mainly involved demethylation events, implying the unusual characteristic of DNA methylation status in 3x watermelon. The present results are valuable to further explore the nature of triploid vigor and autopolyploidizaion in watermelon from the view of epigenetics.

Epigenetics refers to the heritable changes in gene expression without any alteration in DNA sequence, including DNA methylation, histone modification and chromatin conformation. Epigenomics deals with global analyses of epigenetic changes across the entire genome. In the fields of epigenetics and epigenomics, DNA methylation has been drawn a special attention because of its close correlation to human development and carcinogenesis. In recent years, a variety of methods have been developed to study DNA methylation and other epigenetic modification. This review introduces and compares the new methods for epigenomics study and provides useful information for the researcher in this area.

microRNAs (miRNAs) are endogenous, small noncoding RNA molecules discovered in animals, plants and viruses. They play a critical role in developmental and physiological processes and are implicated in the pathogenesis of many human cancers. Presently, human cancer, including colorectal cancer, is recognized as both a genetic and epigenetic disease. Changes induced by miRNAs are considered as epigenetic changes. Experiments were largely performed to analyze the colorectal microRNAome and bio-networking involving miRNAs. This review focuses on recent advances in colorectal miRNA expression profiles. Further, we discuss the regulatory network of miRNAs in the initiation and carcinogenesis of colon cancer in order to open up an avenue of anticancer therapy based on the epigenetic regulation by miRNAs.

Epigenetics refers to the heritable, but reversible, regulation of various biological functions mediated principally through changes in DNA methylation and chromatin structure derived from histone modification. Recent research indicated that epigenetic mechanisms may play vital role in etiology of major psychosis, such as schizophrenia, bipolar disorder and drug addiction. With brief introduction of epigenetic molecular mechanisms and relevance of epigenetics to human common diseases, this review focuses on epigenetic hypothesis and some supporting evidence which are recently emerged in major depressive disorder (MDD).

DNA methylation is an important epigenetic modification and multiple factors interact to regulate the establishment and maintenance of DNA methylation in plant genome. Different methylation sites require different cytosine methyltransferases, which contribute to the modification of chromatin structure and mediate epigenetics with chromatin remodeling enzymes and histone modifying factors. DNA glycosylases can remove DNA methylation and alleviate silencing. The functions and interactions of DNA methylation regulating factors, the establishment, maintenance and removement mechanisms of DNA methylations are reviewed in this paper.

Despite recent successes in cloning various mammals and amphibians, the low efficiency of animals production and abnormal symptoms in many cloned animals are crucial problems in cloning technology. To overcome these problems, scientists focus on mechanisms of cloning. A possible cause of the low success frequency of cloning is the insufficient dedifferentiation and the inadequate reprogramming of the high differentiated adult somatic nucleus in enucleated oocytes, which caused by incomplete methylation and premature de novo remethylation of donor DNA. In cloned embryos the methylation level is higher than normal embryos, and this may cause aberrant expression of several important genes, especially imprinting genes. Study on these mechanisms is very important to improve the rate of successful cloned animals.