Recent years have witnessed an explosive increase in our knowledge about the epigenetic features in human cancers. It became apparent that pancreatic cancer, additionally to its genetic background, is an epigenetic disease characterized by widespread alterations in DNA methylation, histone modification and recruitment of microRNAs. Although more and more in-depth research is performed and epigenetic modifications are shown in healthy and degenerated cells, we still lack insight into how epigenetic modifications are orchestrated during carcinogenesis. By introducing nuclear factor of activated T cell proteins and their impact on gene activation and silencing in pancreatic cancer, this review cites an example of how deregulated oncogenes modulate epigenetic alterations in epithelial cancers.
{"title":"Nuclear Factor of Activated T Cells Operates as Conductor of the Epigenetic Orchestra in Pancreatic Carcinogenesis","authors":"E. Hessmann, V. Ellenrieder","doi":"10.1159/000355617","DOIUrl":"https://doi.org/10.1159/000355617","url":null,"abstract":"Recent years have witnessed an explosive increase in our knowledge about the epigenetic features in human cancers. It became apparent that pancreatic cancer, additionally to its genetic background, is an epigenetic disease characterized by widespread alterations in DNA methylation, histone modification and recruitment of microRNAs. Although more and more in-depth research is performed and epigenetic modifications are shown in healthy and degenerated cells, we still lack insight into how epigenetic modifications are orchestrated during carcinogenesis. By introducing nuclear factor of activated T cell proteins and their impact on gene activation and silencing in pancreatic cancer, this review cites an example of how deregulated oncogenes modulate epigenetic alterations in epithelial cancers.","PeriodicalId":90260,"journal":{"name":"Medical epigenetics","volume":"1 1","pages":"93 - 99"},"PeriodicalIF":0.0,"publicationDate":"2013-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000355617","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"64680966","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M. Kumar, R. Hemalatha, Rajesh Kumar, R. Nagpal, J. P. Devraj, V. Verma, P. Behare, G. Mal, B. Singh
Colorectal cancer (CRC) is a common epithelial neoplasia across the globe, with about 1.2 million newly diagnosed cases and over 600,000 mortalities annually. The underlying causes are numerous including dietary ingredients, environmental factors and gut metabolome that affect colon cellular gene regulation and post-translational modifications of the proteome. Collectively, these alterations initiate epigenetic modifications leading to the inception of various metabolic diseases and malignancies. Epigenetics is at the core of modern medicine since it deals with complex processes that turn the expression of certain genes on and off, and it elucidates the mechanisms and connections between genotypes and the environment during various stages of life. However, the majority of the vertical molecular mechanisms with reference to epigenomics, epigenetic and metabolic ailments are still unidentified and need further research. This article summarizes the burgeoning role of probiotic metabolites and some prominent therapeutic dietary ingredients in the management of CRC.
{"title":"Epigenetics, Probiotic Metabolites and Colon Cancer Prevention: An Overview of Progress, Opportunities and Challenges","authors":"M. Kumar, R. Hemalatha, Rajesh Kumar, R. Nagpal, J. P. Devraj, V. Verma, P. Behare, G. Mal, B. Singh","doi":"10.1159/000354719","DOIUrl":"https://doi.org/10.1159/000354719","url":null,"abstract":"Colorectal cancer (CRC) is a common epithelial neoplasia across the globe, with about 1.2 million newly diagnosed cases and over 600,000 mortalities annually. The underlying causes are numerous including dietary ingredients, environmental factors and gut metabolome that affect colon cellular gene regulation and post-translational modifications of the proteome. Collectively, these alterations initiate epigenetic modifications leading to the inception of various metabolic diseases and malignancies. Epigenetics is at the core of modern medicine since it deals with complex processes that turn the expression of certain genes on and off, and it elucidates the mechanisms and connections between genotypes and the environment during various stages of life. However, the majority of the vertical molecular mechanisms with reference to epigenomics, epigenetic and metabolic ailments are still unidentified and need further research. This article summarizes the burgeoning role of probiotic metabolites and some prominent therapeutic dietary ingredients in the management of CRC.","PeriodicalId":90260,"journal":{"name":"Medical epigenetics","volume":"1 1","pages":"60 - 69"},"PeriodicalIF":0.0,"publicationDate":"2013-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000354719","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"64673830","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Epigenetic mechanisms are essential for normal development during embryogenesis and for differentiation of neural cells. Thus, precise understanding of epigenetic mechanisms, including DNA methylation and histone modification, is important to elucidate the pathogenic pathways in neurodevelopmental disorders. These include various congenital disorders caused by failures of genomic imprinting, X chromosome inactivation, and mutations of the proteins associated with epigenetic gene regulation. Several lines of evidence have suggested that various environmental factors, including insufficient nutrition, drugs, and mental stress, can alter epigenetic gene regulation in the brain, which potentially cause autism and adult mental disorders. However, epigenetic mechanisms are reversible mechanisms based on the attachment and detachment of modification factors onto DNA and histone proteins. Furthermore, recent studies indicate that epigenetic proteins, such as MeCP2, act as ‘lubricants' rather than essential parts that make up the brain structure, which works at a relatively later period of brain development. Therefore, making use of this epigenetic reversibility, the correction of abnormal epigenomic patterns and the administration or upregulation of epigenetic molecules will potentially be useful therapies for neurodevelopmental and mental disorders caused by epigenetic abnormalities.
{"title":"Epigenetics in Neurodevelopmental and Mental Disorders","authors":"T. Kubota, Kunio Miyake, T. Hirasawa","doi":"10.1159/000354718","DOIUrl":"https://doi.org/10.1159/000354718","url":null,"abstract":"Epigenetic mechanisms are essential for normal development during embryogenesis and for differentiation of neural cells. Thus, precise understanding of epigenetic mechanisms, including DNA methylation and histone modification, is important to elucidate the pathogenic pathways in neurodevelopmental disorders. These include various congenital disorders caused by failures of genomic imprinting, X chromosome inactivation, and mutations of the proteins associated with epigenetic gene regulation. Several lines of evidence have suggested that various environmental factors, including insufficient nutrition, drugs, and mental stress, can alter epigenetic gene regulation in the brain, which potentially cause autism and adult mental disorders. However, epigenetic mechanisms are reversible mechanisms based on the attachment and detachment of modification factors onto DNA and histone proteins. Furthermore, recent studies indicate that epigenetic proteins, such as MeCP2, act as ‘lubricants' rather than essential parts that make up the brain structure, which works at a relatively later period of brain development. Therefore, making use of this epigenetic reversibility, the correction of abnormal epigenomic patterns and the administration or upregulation of epigenetic molecules will potentially be useful therapies for neurodevelopmental and mental disorders caused by epigenetic abnormalities.","PeriodicalId":90260,"journal":{"name":"Medical epigenetics","volume":"1 1","pages":"52 - 59"},"PeriodicalIF":0.0,"publicationDate":"2013-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000354718","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"64673621","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
In the past decades, studies on twins have had a great impact on dissecting the genetic and environmental contributions to human diseases and complex traits. In the era of functional genomics, the valuable samples of twins help to bridge the gap between gene activity and environmental conditions through multiple epigenetic mechanisms. This paper reviews the new developments in using twins to study disease-related epigenetic alterations, links them to lifetime environmental exposure with a focus on the discordant twin design and proposes novel data-analytical approaches with the aim of promoting a more efficient use of twins in epigenetic studies of complex human diseases.
{"title":"Epigenetic Epidemiology of Complex Diseases Using Twins","authors":"Q. Tan","doi":"10.1159/000354285","DOIUrl":"https://doi.org/10.1159/000354285","url":null,"abstract":"In the past decades, studies on twins have had a great impact on dissecting the genetic and environmental contributions to human diseases and complex traits. In the era of functional genomics, the valuable samples of twins help to bridge the gap between gene activity and environmental conditions through multiple epigenetic mechanisms. This paper reviews the new developments in using twins to study disease-related epigenetic alterations, links them to lifetime environmental exposure with a focus on the discordant twin design and proposes novel data-analytical approaches with the aim of promoting a more efficient use of twins in epigenetic studies of complex human diseases.","PeriodicalId":90260,"journal":{"name":"Medical epigenetics","volume":"1 1","pages":"46 - 51"},"PeriodicalIF":0.0,"publicationDate":"2013-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000354285","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"64671953","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
It is known that tumor cells undergo genetic and epigenetic alterations. Recent evidence suggests that epigenetic changes in the tumor microenvironment play a significant role in carcinogenesis. In this brief review, we discuss the epigenetic changes of the microenvironment in different malignancies and their clinical significance.
{"title":"Epigenetics Meets the Tumor Microenvironment","authors":"P. Dey","doi":"10.1159/000354283","DOIUrl":"https://doi.org/10.1159/000354283","url":null,"abstract":"It is known that tumor cells undergo genetic and epigenetic alterations. Recent evidence suggests that epigenetic changes in the tumor microenvironment play a significant role in carcinogenesis. In this brief review, we discuss the epigenetic changes of the microenvironment in different malignancies and their clinical significance.","PeriodicalId":90260,"journal":{"name":"Medical epigenetics","volume":"1 1","pages":"31 - 36"},"PeriodicalIF":0.0,"publicationDate":"2013-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000354283","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"64671113","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Patho-epigenetics is a new discipline dealing with the description of pathologic changes elicited by epigenetic dysregulation. Patho-epigenetic processes contribute to the development of both rare syndromes and diseases of high prevalence in human populations. In this short review, we summarize the basic epigenetic regulatory mechanisms in a nutshell and briefly outline how epigenetic reprogramming contributes to all forms of tumorigenesis and plays a role both in the initiation and progression of neoplasms.
{"title":"Patho-Epigenetics","authors":"J. Minárovits, H. Niller","doi":"10.1159/000354284","DOIUrl":"https://doi.org/10.1159/000354284","url":null,"abstract":"Patho-epigenetics is a new discipline dealing with the description of pathologic changes elicited by epigenetic dysregulation. Patho-epigenetic processes contribute to the development of both rare syndromes and diseases of high prevalence in human populations. In this short review, we summarize the basic epigenetic regulatory mechanisms in a nutshell and briefly outline how epigenetic reprogramming contributes to all forms of tumorigenesis and plays a role both in the initiation and progression of neoplasms.","PeriodicalId":90260,"journal":{"name":"Medical epigenetics","volume":"1 1","pages":"37 - 45"},"PeriodicalIF":0.0,"publicationDate":"2013-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000354284","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"64671266","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The innate immune response acts in a myriad of ways to protect the host from pathogenic agents. This interplay requires changes in gene expression patterns that allow the host to effectively respond. Epigenetic mechanisms are important in this scenario. Understanding these mechanisms is of great interest for the development of appropriate therapies modulating the immune response. One of the important receptor families responsible for the activity of the innate immune system is the Toll-like receptor (TLR) family. This family is important for the innate immune response to infections and has been implicated to play a role in cancer. Understanding the epigenetic mechanisms regulated by TLR signaling is important for the development of novel therapies for a multitude of diseases including cancer. In this article, we present an overview of this pathway and its role in carcinogenesis, and we discuss the epigenetic mechanisms regulating its activity.
{"title":"Epigenetic Regulation of Toll-Like Receptor Signaling: Implications for Cancer Development","authors":"Shannon K. Boi, S. Elsawa","doi":"10.1159/000353684","DOIUrl":"https://doi.org/10.1159/000353684","url":null,"abstract":"The innate immune response acts in a myriad of ways to protect the host from pathogenic agents. This interplay requires changes in gene expression patterns that allow the host to effectively respond. Epigenetic mechanisms are important in this scenario. Understanding these mechanisms is of great interest for the development of appropriate therapies modulating the immune response. One of the important receptor families responsible for the activity of the innate immune system is the Toll-like receptor (TLR) family. This family is important for the innate immune response to infections and has been implicated to play a role in cancer. Understanding the epigenetic mechanisms regulated by TLR signaling is important for the development of novel therapies for a multitude of diseases including cancer. In this article, we present an overview of this pathway and its role in carcinogenesis, and we discuss the epigenetic mechanisms regulating its activity.","PeriodicalId":90260,"journal":{"name":"Medical epigenetics","volume":"1 1","pages":"19 - 30"},"PeriodicalIF":0.0,"publicationDate":"2013-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000353684","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"64666736","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Monozygotic twins share an identical DNA sequence but typically display some level of phenotypic discordance. The cause of this discordance is often unknown. Two known contributing factors to phenotype are genetics and environment. While the mechanism for the genetic effect is defined through DNA sequence, the mechanism for expression of the environmental effect is less defined. With the emergence of the field of epigenetics, researchers have begun to consider it an important contributing factor to phenotype. Exposure to various environmental factors has been shown to have an effect on an individual's epigenetic marks and may be the primary mechanism for how the environment induces a change in phenotype. Current research indicates that epigenetic differences between monozygotic twins may be an important contributing factor to phenotypic discordance. Monozygotic twins are an ideal resource for the study of epigenetics since many confounding factors found in the general population, such as variation in DNA sequence, can be eliminated. Uncovering these epigenetic factors will increase our understanding of the molecular mechanisms that may contribute to phenotypic discordance in monozygotic twins and may lead to new theoretical and experimental opportunities in health and disease.
{"title":"Epigenetics as the Underlying Mechanism for Monozygotic Twin Discordance","authors":"Tara L. Hogenson","doi":"10.1159/000353688","DOIUrl":"https://doi.org/10.1159/000353688","url":null,"abstract":"Monozygotic twins share an identical DNA sequence but typically display some level of phenotypic discordance. The cause of this discordance is often unknown. Two known contributing factors to phenotype are genetics and environment. While the mechanism for the genetic effect is defined through DNA sequence, the mechanism for expression of the environmental effect is less defined. With the emergence of the field of epigenetics, researchers have begun to consider it an important contributing factor to phenotype. Exposure to various environmental factors has been shown to have an effect on an individual's epigenetic marks and may be the primary mechanism for how the environment induces a change in phenotype. Current research indicates that epigenetic differences between monozygotic twins may be an important contributing factor to phenotypic discordance. Monozygotic twins are an ideal resource for the study of epigenetics since many confounding factors found in the general population, such as variation in DNA sequence, can be eliminated. Uncovering these epigenetic factors will increase our understanding of the molecular mechanisms that may contribute to phenotypic discordance in monozygotic twins and may lead to new theoretical and experimental opportunities in health and disease.","PeriodicalId":90260,"journal":{"name":"Medical epigenetics","volume":"1 1","pages":"3 - 18"},"PeriodicalIF":0.0,"publicationDate":"2013-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000353688","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"64666967","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 1900-01-01DOI: 10.1016/b978-0-12-823928-5.00027-x
Maricarmen Colón-Díaz, Alexander J. Jaramillo, Edwin Y. Soto, Perla M. Elosegui
{"title":"Reproductive disease epigenetics","authors":"Maricarmen Colón-Díaz, Alexander J. Jaramillo, Edwin Y. Soto, Perla M. Elosegui","doi":"10.1016/b978-0-12-823928-5.00027-x","DOIUrl":"https://doi.org/10.1016/b978-0-12-823928-5.00027-x","url":null,"abstract":"","PeriodicalId":90260,"journal":{"name":"Medical epigenetics","volume":"93 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"1900-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"53908616","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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