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Epigenetic Diagnosis & Therapy - Current Issue
Volume 1, Issue 2, 2015
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Epigenetic MicroRNA Regulation of Multiple Chromatin Functions: A Perspective in Cancer
MicroRNAs (miRNAs) are a group of small noncoding RNAs of about 19-25 nucleotides (nt) in length. miRNAs act as a binary switch and play a key role in RNAi-mediated gene silencing by inhibiting translation and/or triggering subsequent degradation of their target mRNAs. Recent advances in the field of molecular biology have highlighted the role of miRNAs in different biological functions, including embryogenesis, developmental pattern formation and differentiation, organogenesis, growth control and cell death like brain development, including patterning, neurogenesis, neuronal differentiation, subtype specification, and neuronal activity which is scripted via menus. DNA methylation and Histone modifications facilitating epigenetic manipulations in the genome were already a precursor for tumorigenic development. But recently miRNA mediated regulatory mechanisms also have been implicated in malignancy by regulation of DNA methyltion. Keeping these facts in mind, we have summarized the emerging roles of miRNAs in modulating gene function and affecting signaling pathways. We have tried to focus into cancer cell physiology caused by miRNA mediated processes, and discuss the precise roles of miRNAs in modulating both DNA methylation and histone modifications.
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A Role for Epigenetics in Broadening the Scope of Pediatric Care in the Prevention of Adolescent Smoking
Authors: Steven R.H. Beach, Meg Gerrard, Frederick X. Gibbons, Gene H. Brody and Robert A. PhilibertAdolescence presents a critical opportunity to support the development of healthy patterns of behavior and prevent future health problems. Unfortunately, there is not yet a well-developed prevention model that allows pediatricians to initiate and monitor prevention efforts for the substantial minority of individuals who engage in risky behavior during adolescence. We suggest that recently developed epigenetic technologies may provide a bridge to a new prevention paradigm in which pediatricians screen for indicated smoking prevention services. Specifically, since currently available tobacco use screening measures are insensitive to low levels of use, newly developed methylation based approaches may enhance the sensitivity of the initial screening for nascent smoking behavior as well monitoring of outcomes. We conclude that the incorporation of Next Gen screening technologies into standard pediatric evaluations may allow for more effective referral to prevention programming for tobacco use. In addition to the potential direct impact on long-term enhancement of health outcomes secondary to smoking prevention, well-established links between smoking and other risk behaviors suggest that expanded referral for nascent smoking may also create opportunities to address other risky adolescent behaviors, and so decrease several interrelated drivers of long-term health care costs.
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Epivention: Epigenetic Based Cancer Chemoprevention
Authors: Hui Wang, Jin Lu, Xiaoyong Tong, Xin Wang, Min Wang, Sufang Zhou, Zhenxiang An, Jinhua Wang and Wanzhou ZhaoThe new term "epivention" refers to epigenetic based cancer chemoprevention targeting epigenetic alterations caused by heritable, but potentially reversible, changes in DNA methylation and chromatin structure. Epigenetic alterations in cancer initiation, promotion, and progression stages, has gained increasing attention. Epigenetic alterations such as DNA methylation, histone modifications and microRNA play an important role in carcinogenesis. Targeting the epigenetic alterations with compounds that regulate DNA methylation, histone modifications, and microRNA profiles in carcinogenesis provides an evolving strategy for cancer chemoprevention. In the review, we focus on the importance of epigenetic mechanisms for gene regulation in cancer chemoprevention and the impact of the ingredients from traditional Chinese medicines that exert epivention effect.
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The Role of Epigenetics in Drug Resistance in Cancer
Authors: Alexandra B. Lantermann, Kaitlin J. McCutcheon and Sreenath V. SharmaResistance of malignant cells to chemotherapy and molecularly targeted therapy is a major roadblock in our effort to cure cancer. A variety of underlying mechanisms have been described, some of which are shared between resistance to chemotherapy and resistance to molecularly targeted therapy. Although the influence of genetic mutations in the development of drug resistance is beyond question, many examples now support the contribution of epigenetic changes to drug resistance. Several clinical trials are under way to explore the effectiveness of epigenetics-targeting drugs to reverse or overcome resistance to cancer therapies. In addition to these strategies, we suggest a complementary approach that could utilize epigenetics-targeting drugs to prevent drug resistance.
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Epigenetic Modulation: A Promising Avenue to Advance Hematopoietic Stem Cell-Based Therapy for Severe Autoimmune Disorders
More LessSevere autoimmune disorders, such as certain serious forms of multiple sclerosis, rheumatoid arthritis, and systemic lupus erythematosus, lead to poor prognosis for patients and can be fatal. Traditional immunosuppression therapies are rarely curative but only temporarily relieve patients from the flares. Arising “epigenetic” medications may enhance specificity but limitations still exist for their applications to severe autoimmune disorders due to the medications targeting differentiated immune cells. Hematopoietic stem cell-based therapy represents a different therapeutic strategy, which aims to reconstitute the functionality of the whole immune system. Such a re-constitutive approach has demonstrated long-lasting clinical benefits. Currently, hematopoietic stem cell transplantation remains a challenging and risky procedure, but recent scientific discoveries indicate that targeting epigenetics in hematopoietic stem cells bears promise to improve both the success rate and safety profile of hematopoietic stem cell-based therapy for treating severe autoimmune disorders.
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Do Chromatin Interaction Networks Radiate Pathogenic Contagion in the Genome?
More LessIt is being recognized that the eukaryotic genome physically interacts with itself via a complex network of long range chromatin interactions. While the insights to the underlying organizing principles are being worked out, an interesting and rather provocative theme which is emerging is that the genes can cross-talk to influence each others’ epigenetic states. If firmly established, this observation would endow a novel perspective to the genetic and epigenetic basis of disease development. In this letter, I discuss the present evidence and implications of long-range regulatory cross-talk among genes.
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Transcription Coupled DNA Methylation Mediated by RNA Pol II and DNMT1
Transcriptional gene silencing is mediated by various epigenetic modifications including DNA methylation, histone modifications and recruitment of binding proteins that reads the methyl and other modification marks. The order in which these modifications occur followed by repressor protein recruitment remains contentious. Here, using purified protein components, we show that mammalian RNA polymerase II (RNA Pol II) is involved in DNA methylation control. DNA (cytosine-5) methyltransferase 1 (DNMT1) colocalizes, directly interacts and binds to the phosphorylated C-terminal repeat domain (CTD) of Rpb1, a major structural subunit of RNA Pol II. The association of RNA Pol II with DNMT1 during transcription enhances DNA methylation, and methylated DNA doesn’t affect in vitro transcription. Addition of methyl CpG binding protein 2 (MeCP2), inhibited in vitro transcription of DNA in a methylation dependent manner, suggesting a possible mechanism for RNA Pol II coupled transcriptional silencing mediated by DNMT1 and MeCP2.
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