Pub Date : 2021-01-01DOI: 10.1016/b978-0-12-823928-5.00012-8
J. Tajbakhsh, J. Singh
{"title":"Epigenetics in toxicology and drug development","authors":"J. Tajbakhsh, J. Singh","doi":"10.1016/b978-0-12-823928-5.00012-8","DOIUrl":"https://doi.org/10.1016/b978-0-12-823928-5.00012-8","url":null,"abstract":"","PeriodicalId":90260,"journal":{"name":"Medical epigenetics","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"53908056","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 : 2021-01-01DOI: 10.1016/b978-0-12-823928-5.00030-x
C. Abi Khalil
{"title":"Cardiovascular disorders and epigenetics","authors":"C. Abi Khalil","doi":"10.1016/b978-0-12-823928-5.00030-x","DOIUrl":"https://doi.org/10.1016/b978-0-12-823928-5.00030-x","url":null,"abstract":"","PeriodicalId":90260,"journal":{"name":"Medical epigenetics","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"53908191","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 : 2021-01-01DOI: 10.1016/b978-0-12-823928-5.00037-2
Patricia Chaves, J. L. Onieva, I. Barragán
{"title":"Epigenetic biomarkers of disease","authors":"Patricia Chaves, J. L. Onieva, I. Barragán","doi":"10.1016/b978-0-12-823928-5.00037-2","DOIUrl":"https://doi.org/10.1016/b978-0-12-823928-5.00037-2","url":null,"abstract":"","PeriodicalId":90260,"journal":{"name":"Medical epigenetics","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"53908220","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 : 2021-01-01DOI: 10.1016/b978-0-12-823928-5.00019-0
D. Ehnes, S. Levy, H. Ruohola-Baker
{"title":"Epigenetics and regenerative medicine","authors":"D. Ehnes, S. Levy, H. Ruohola-Baker","doi":"10.1016/b978-0-12-823928-5.00019-0","DOIUrl":"https://doi.org/10.1016/b978-0-12-823928-5.00019-0","url":null,"abstract":"","PeriodicalId":90260,"journal":{"name":"Medical epigenetics","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"53908268","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}
A. Fodor, A. Rusu, G. Roman, Ramona Suharoschi, R. Vulturar, A. Sitar-Tăut, A. Cozma
{"title":"Prognostic Epigenetics","authors":"A. Fodor, A. Rusu, G. Roman, Ramona Suharoschi, R. Vulturar, A. Sitar-Tăut, A. Cozma","doi":"10.1016/c2017-0-00973-4","DOIUrl":"https://doi.org/10.1016/c2017-0-00973-4","url":null,"abstract":"","PeriodicalId":90260,"journal":{"name":"Medical epigenetics","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54155409","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 : 2016-07-01DOI: 10.1016/B978-0-12-803239-8.00012-0
S. Mehta, K. Jeffrey
{"title":"Immune System Disorders and Epigenetics","authors":"S. Mehta, K. Jeffrey","doi":"10.1016/B978-0-12-803239-8.00012-0","DOIUrl":"https://doi.org/10.1016/B978-0-12-803239-8.00012-0","url":null,"abstract":"","PeriodicalId":90260,"journal":{"name":"Medical epigenetics","volume":"121 1","pages":"199 - 219"},"PeriodicalIF":0.0,"publicationDate":"2016-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/B978-0-12-803239-8.00012-0","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54168067","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 GABAergic neurotransmission is a highly conserved system that has been attributed to various regulatory events. There has been a notable number of studies on the importance of GABAergic neurotransmission, both excitatory and inhibitory, in neurogenesis and central nervous system development including its control of neuronal cell proliferation and migration, synaptogenesis, dendrite formation and branching, and new neuronal cell integration in the adult brain. There has been remarkable progress in understanding the epigenetic regulations of GABAergic genes and their aberrant expressions in various neurological disorders such as autism spectrum disorder, Rett's syndrome, schizophrenia and PWS. The roles of histone modifications, chromatin looping and gene methylation have been implicated in altered regulations of key genes in the GABAergic pathway. Taken together, they affect the functioning of GABAergic neurotransmission and disrupt various events in brain development. Here, we focus on the role of GABAergic neurotransmission in brain development and on how various genetic and epigenetic events regulate the GABAergic genes in pre- and postnatal brain. We also discuss how these regulatory mechanisms contribute to the pathogenesis of neurological disorders and, therefore, can be used in the development of potential epigenetic therapy for these diseases.
{"title":"Epigenetic Regulations of GABAergic Neurotransmission: Relevance for Neurological Disorders and Epigenetic Therapy","authors":"Shikshya Shrestha, S. Offer","doi":"10.1159/000444713","DOIUrl":"https://doi.org/10.1159/000444713","url":null,"abstract":"The GABAergic neurotransmission is a highly conserved system that has been attributed to various regulatory events. There has been a notable number of studies on the importance of GABAergic neurotransmission, both excitatory and inhibitory, in neurogenesis and central nervous system development including its control of neuronal cell proliferation and migration, synaptogenesis, dendrite formation and branching, and new neuronal cell integration in the adult brain. There has been remarkable progress in understanding the epigenetic regulations of GABAergic genes and their aberrant expressions in various neurological disorders such as autism spectrum disorder, Rett's syndrome, schizophrenia and PWS. The roles of histone modifications, chromatin looping and gene methylation have been implicated in altered regulations of key genes in the GABAergic pathway. Taken together, they affect the functioning of GABAergic neurotransmission and disrupt various events in brain development. Here, we focus on the role of GABAergic neurotransmission in brain development and on how various genetic and epigenetic events regulate the GABAergic genes in pre- and postnatal brain. We also discuss how these regulatory mechanisms contribute to the pathogenesis of neurological disorders and, therefore, can be used in the development of potential epigenetic therapy for these diseases.","PeriodicalId":90260,"journal":{"name":"Medical epigenetics","volume":"4 1","pages":"1 - 19"},"PeriodicalIF":0.0,"publicationDate":"2016-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000444713","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"65050275","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 transcription factor ERG is important during development for vasculogenesis and angiogenesis, blood vessel integrity, and maintenance of hematopoietic stem cells. In human adults, ERG is only expressed in endothelial cells and performs similar roles as in development to mediate blood vessel formation. However, aberrant overexpression of ERG in the adult contributes to diseases like prostate cancer, and the molecular and cellular mechanisms of ERG in tumorigenesis remain largely unclear. Studies of ERG-positive prostate cancers have shown that ERG promotes cell invasion and metastasis and contributes to poor patient prognosis. Together, these studies reveal ERG-mediated cell invasion as a potential link between normal ERG function in development and oncogenic ERG function in prostate cancer.
{"title":"ERG-Mediated Cell Invasion: A Link between Development and Tumorigenesis","authors":"Alexandra M. Blee, Haojie Huang","doi":"10.1159/000440978","DOIUrl":"https://doi.org/10.1159/000440978","url":null,"abstract":"The transcription factor ERG is important during development for vasculogenesis and angiogenesis, blood vessel integrity, and maintenance of hematopoietic stem cells. In human adults, ERG is only expressed in endothelial cells and performs similar roles as in development to mediate blood vessel formation. However, aberrant overexpression of ERG in the adult contributes to diseases like prostate cancer, and the molecular and cellular mechanisms of ERG in tumorigenesis remain largely unclear. Studies of ERG-positive prostate cancers have shown that ERG promotes cell invasion and metastasis and contributes to poor patient prognosis. Together, these studies reveal ERG-mediated cell invasion as a potential link between normal ERG function in development and oncogenic ERG function in prostate cancer.","PeriodicalId":90260,"journal":{"name":"Medical epigenetics","volume":"3 1","pages":"19 - 29"},"PeriodicalIF":0.0,"publicationDate":"2015-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000440978","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"64922774","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}
Abdirashid Shire, Gwen Lomberk, Jin-Ping Lai, Hongzhi Zou, Norihiko Tsuchiya, Ileana Aderca, Catherine D Moser, Kadra H Gulaid, Abdul Oseini, Chunling Hu, Omar Warsame, Robert B Jenkins, Lewis R Roberts
Background: Hepatocellular carcinoma (HCC) is the second most frequent cause of cancer death worldwide. Sulfatase 1 (SULF1) functions as a tumor suppressor in HCC cell lines in vitro, but also has an oncogenic effect in some HCCs in vivo.
Aim: To examine the mechanisms regulating SULF1 and its function in HCC.
Methods: First, SULF1 mRNA and protein expression were examined. Second, we examined SULF1 gene copy number in HCC cells. Third, we assessed whether DNA methylation or methylation and/or acetylation of histone marks on the promoter regulate SULF1 expression. Finally, we examined the effect of 5-Aza-dC on sulfatase activity and drug-induced apoptosis.
Results: SULF1 mRNA was down-regulated in 9/11 HCC cell lines but only 6/10 primary tumors. SULF1 mRNA correlated with protein expression. Gene copy number assessment by fluorescence in situ hybridization showed intact SULF1 alleles in low SULF1 expressing cell lines. CpG island methylation in the SULF1 promoter and two downstream CpG islands did not show an inverse correlation between DNA methylation and SULF1 expression. However, chromatin immunoprecipitation showed that the SULF1 promoter acquires a silenced chromatin state in low SULF1-expressing cells through an increase in di/trimethyl-K9H3 and trimethyl-K27H3 and a concomitant loss of activating acetyl K9, K14H3 marks. 5-Aza-dC restored SULF1 mRNA expression in SULF1-negative cell lines, with an associated increase in sulfatase activity and sensitization of HCC cells to cisplatin-induced apoptosis.
Conclusion: SULF1 gene silencing in HCC occurs through histone modifications on the SULF1 promoter. Restoration of SULF1 mRNA expression by 5-Aza-dC sensitized HCC cells to drug-induced apoptosis.
{"title":"Restoration of epigenetically silenced SULF1 expression by 5-aza-2-deoxycytidine sensitizes hepatocellular carcinoma cells to chemotherapy-induced apoptosis.","authors":"Abdirashid Shire, Gwen Lomberk, Jin-Ping Lai, Hongzhi Zou, Norihiko Tsuchiya, Ileana Aderca, Catherine D Moser, Kadra H Gulaid, Abdul Oseini, Chunling Hu, Omar Warsame, Robert B Jenkins, Lewis R Roberts","doi":"10.1159/000375461","DOIUrl":"https://doi.org/10.1159/000375461","url":null,"abstract":"<p><strong>Background: </strong>Hepatocellular carcinoma (HCC) is the second most frequent cause of cancer death worldwide. Sulfatase 1 (SULF1) functions as a tumor suppressor in HCC cell lines <i>in vitro</i>, but also has an oncogenic effect in some HCCs <i>in vivo</i>.</p><p><strong>Aim: </strong>To examine the mechanisms regulating SULF1 and its function in HCC.</p><p><strong>Methods: </strong>First, SULF1 mRNA and protein expression were examined. Second, we examined SULF1 gene copy number in HCC cells. Third, we assessed whether DNA methylation or methylation and/or acetylation of histone marks on the promoter regulate SULF1 expression. Finally, we examined the effect of 5-Aza-dC on sulfatase activity and drug-induced apoptosis.</p><p><strong>Results: </strong>SULF1 mRNA was down-regulated in 9/11 HCC cell lines but only 6/10 primary tumors. SULF1 mRNA correlated with protein expression. Gene copy number assessment by fluorescence <i>in situ</i> hybridization showed intact SULF1 alleles in low SULF1 expressing cell lines. CpG island methylation in the SULF1 promoter and two downstream CpG islands did not show an inverse correlation between DNA methylation and SULF1 expression. However, chromatin immunoprecipitation showed that the SULF1 promoter acquires a silenced chromatin state in low SULF1-expressing cells through an increase in di/trimethyl-K9H3 and trimethyl-K27H3 and a concomitant loss of activating acetyl K9, K14H3 marks. 5-Aza-dC restored SULF1 mRNA expression in SULF1-negative cell lines, with an associated increase in sulfatase activity and sensitization of HCC cells to cisplatin-induced apoptosis.</p><p><strong>Conclusion: </strong>SULF1 gene silencing in HCC occurs through histone modifications on the <i>SULF1</i> promoter. Restoration of SULF1 mRNA expression by 5-Aza-dC sensitized HCC cells to drug-induced apoptosis.</p>","PeriodicalId":90260,"journal":{"name":"Medical epigenetics","volume":"3 1","pages":"1-18"},"PeriodicalIF":0.0,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000375461","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33957548","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
4-1BB, a master regulator of our defense system, is present on several kinds of immune cells and has different functions in immune responses based on specific conditions. An expression of this molecule on T lymphocytes, antigen-presenting cells (APCs) and pathogenic cells directs immune responses by a costimulatory signal of 4-1BB and its ligand, 4-1BBL. Under abnormal conditions, such as inflammation and hypoxia, 4-1BB and 4-1BBL are also induced on nonimmune cells including epithelial cells, endothelial cells, smooth muscle cells, and cardiac myocytes. Recently, 4-1BB has been found on brite adipocytes; it is identified as a specific marker for this type of fat cells. An increase in acetylated histone by histone deacetylase inhibitors (HDACi) leads to an elevation of 4-1BB and 4-1BBL expression and major histocompatibility complex expression on T-cell lymphoma and other tumor cell lines, which enhance the activities of APCs and cytotoxic T lymphocytes to improve antitumor immune responses. Conversely, 4-1BB signaling triggered by a soluble 4-1BB receptor or anti-4-1BB antibodies strengthens the anticancer effect of HDACi by regulating both effector and regulatory T cells. Therefore, further investigations into the epigenetic regulations of 4-1BB/4-1BBL interaction will give us more meaningful information to develop new methods to prevent disorders in human beings such as cancer, obesity, autoimmune and infectious diseases.
{"title":"4-1BB and the Epigenetic Regulations of This Molecule","authors":"Thien Chu-Dinh, Dinh-Toi Chu","doi":"10.1159/000368900","DOIUrl":"https://doi.org/10.1159/000368900","url":null,"abstract":"4-1BB, a master regulator of our defense system, is present on several kinds of immune cells and has different functions in immune responses based on specific conditions. An expression of this molecule on T lymphocytes, antigen-presenting cells (APCs) and pathogenic cells directs immune responses by a costimulatory signal of 4-1BB and its ligand, 4-1BBL. Under abnormal conditions, such as inflammation and hypoxia, 4-1BB and 4-1BBL are also induced on nonimmune cells including epithelial cells, endothelial cells, smooth muscle cells, and cardiac myocytes. Recently, 4-1BB has been found on brite adipocytes; it is identified as a specific marker for this type of fat cells. An increase in acetylated histone by histone deacetylase inhibitors (HDACi) leads to an elevation of 4-1BB and 4-1BBL expression and major histocompatibility complex expression on T-cell lymphoma and other tumor cell lines, which enhance the activities of APCs and cytotoxic T lymphocytes to improve antitumor immune responses. Conversely, 4-1BB signaling triggered by a soluble 4-1BB receptor or anti-4-1BB antibodies strengthens the anticancer effect of HDACi by regulating both effector and regulatory T cells. Therefore, further investigations into the epigenetic regulations of 4-1BB/4-1BBL interaction will give us more meaningful information to develop new methods to prevent disorders in human beings such as cancer, obesity, autoimmune and infectious diseases.","PeriodicalId":90260,"journal":{"name":"Medical epigenetics","volume":"70 1","pages":"80 - 85"},"PeriodicalIF":0.0,"publicationDate":"2014-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000368900","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"64750492","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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