Progress in drug research. Fortschritte der Arzneimittelforschung. Progres des recherches pharmaceutiques最新文献_第8页

Genome-wide epigenetic modifications in cancer. 癌症的全基因组表观遗传修饰。

Progress in drug research. Fortschritte der Arzneimittelforschung. Progres des recherches pharmaceutiques Pub Date : 2011-01-01 DOI: 10.1007/978-3-7643-8989-5_2

Yoon Jung Park, Rainer Claus, Dieter Weichenhan, Christoph Plass

{"title":"Genome-wide epigenetic modifications in cancer.","authors":"Yoon Jung Park, Rainer Claus, Dieter Weichenhan, Christoph Plass","doi":"10.1007/978-3-7643-8989-5_2","DOIUrl":"https://doi.org/10.1007/978-3-7643-8989-5_2","url":null,"abstract":"Epigenetic alterations in cancer include changes in DNA methylation and associated histone modifications that influence the chromatin states and impact gene expression patterns. Due to recent technological advantages, the scientific community is now obtaining a better picture of the genome-wide epigenetic changes that occur in a cancer genome. These epigenetic alterations are associated with chromosomal instability and changes in transcriptional control which influence the overall gene expression differences seen in many human malignancies. In this review, we will briefly summarize our current knowledge of the epigenetic patterns and mechanisms of gene regulation in healthy tissues and relate this to what is known for cancer genomes. Our focus will be on DNA methylation. We will review the current standing of technologies that have been developed over recent years. This field is experiencing a revolution in the strategies used to measure epigenetic alterations, which includes the incorporation of next generation sequencing tools. We also will review strategies that utilize epigenetic information for translational purposes, with a special emphasis on the potential use of DNA methylation marks for early disease detection and prognosis. The review will close with an outlook on challenges that this field is facing.","PeriodicalId":20603,"journal":{"name":"Progress in drug research. Fortschritte der Arzneimittelforschung. Progres des recherches pharmaceutiques","volume":"67 ","pages":"25-49"},"PeriodicalIF":0.0,"publicationDate":"2011-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/978-3-7643-8989-5_2","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29521390","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}

引用次数: 54

Transcriptional regulatory networks in embryonic stem cells. 胚胎干细胞的转录调控网络。

Progress in drug research. Fortschritte der Arzneimittelforschung. Progres des recherches pharmaceutiques Pub Date : 2011-01-01 DOI: 10.1007/978-3-7643-8989-5_12

Yun Shen Chan, Lin Yang, Huck-Hui Ng

{"title":"Transcriptional regulatory networks in embryonic stem cells.","authors":"Yun Shen Chan, Lin Yang, Huck-Hui Ng","doi":"10.1007/978-3-7643-8989-5_12","DOIUrl":"https://doi.org/10.1007/978-3-7643-8989-5_12","url":null,"abstract":"Transcriptional regulation is one of the most fundamental processes in biology, governing the morphology, function, and behavior of cells and thus the survival of organisms. The embryonic stem cell (ESC) provides a good model for the understanding of transcriptional regulation in vertebrate systems. Recent efforts have led to the identification of molecular events, which confer upon these cells the unique properties of pluripotency and self renewal. The core regulatory network maintaining the ESC identity involves three master regulators: Oct4, Sox2, and Nanog. Large-scale mapping studies interrogating the binding sites of these and other transcription factors showed co-occupancy of distinct sets of transcription factors. The assembly of multitranscription factor complexes could serve as a mechanism for providing specificity in regulating ESC-specific gene expression. These studies are also beginning to unravel the transcriptional regulatory networks that govern the ESC identity. Loss-of-function RNAi screens also identified novel regulatory molecules involved in the stable propagation of the ESC state. This argues for an ESC transcriptional regulation program in which interconnected transcriptional regulatory networks involving large numbers of transcription factors and epigenetic modifiers work in concert on ESC- and differentiation-specific genes to achieve cell state stability. This chapter traces the major efforts made over the past decade in dissecting the transcriptional regulatory network governing ESC identity and offers perspectives on the future directions of the field.","PeriodicalId":20603,"journal":{"name":"Progress in drug research. Fortschritte der Arzneimittelforschung. Progres des recherches pharmaceutiques","volume":"67 ","pages":"239-52"},"PeriodicalIF":0.0,"publicationDate":"2011-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/978-3-7643-8989-5_12","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29521330","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}

引用次数: 75

DNA methylation and cancer. DNA甲基化和癌症。

Progress in drug research. Fortschritte der Arzneimittelforschung. Progres des recherches pharmaceutiques Pub Date : 2011-01-01 DOI: 10.1007/978-3-7643-8989-5_1

Phillippa C Taberlay, Peter A Jones

{"title":"DNA methylation and cancer.","authors":"Phillippa C Taberlay, Peter A Jones","doi":"10.1007/978-3-7643-8989-5_1","DOIUrl":"https://doi.org/10.1007/978-3-7643-8989-5_1","url":null,"abstract":"DNA methylation acts in concert with other epigenetic mechanisms to regulate normal gene expression and facilitate chromatin organization within cells. Aberrant DNA methylation patterns are acquired during carcinogenic transformation; such events are often accompanied by alterations in chromatin structure at gene regulatory regions. The expression pattern of any given gene is achieved by interacting epigenetic mechanisms. First, the insertion of nucleosomes at transcriptional start sites prevents the binding of the transcriptional machinery and additional cofactors that initiate gene expression. Second, nucleosomes anchor all of the DNMT3A and DNMT3B methyltransferase proteins in the cell, which suggests a role for histone octamers in the establishment of DNA methylation patterns. During carcinogenesis, epigenetic switching and 5-methylcytosine reprogramming result in the aberrant hypermethylation of CpG islands, reducing epigenetic plasticity of critical developmental and tumor suppressor genes, rendering them unresponsive to normal stimuli. Here, we will discuss the importance of both established and novel molecular concepts that may underlie the role of DNA methylation in cancer.","PeriodicalId":20603,"journal":{"name":"Progress in drug research. Fortschritte der Arzneimittelforschung. Progres des recherches pharmaceutiques","volume":"67 ","pages":"1-23"},"PeriodicalIF":0.0,"publicationDate":"2011-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/978-3-7643-8989-5_1","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29521388","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}

引用次数: 59

Epigenetic mechanisms of mental retardation. 智力迟钝的表观遗传机制。

Progress in drug research. Fortschritte der Arzneimittelforschung. Progres des recherches pharmaceutiques Pub Date : 2011-01-01 DOI: 10.1007/978-3-7643-8989-5_7

Anne Schaefer, Alexander Tarakhovsky, Paul Greengard

引用次数: 13

Epigenetics and disease: pharmaceutical opportunities. Preface. 表观遗传学和疾病:制药机会。前言。

Progress in drug research. Fortschritte der Arzneimittelforschung. Progres des recherches pharmaceutiques Pub Date : 2011-01-01

Susan M Gasser, En Li

引用次数: 0

HDAC inhibitors and cancer therapy. HDAC抑制剂和癌症治疗。

Progress in drug research. Fortschritte der Arzneimittelforschung. Progres des recherches pharmaceutiques Pub Date : 2011-01-01 DOI: 10.1007/978-3-7643-8989-5_9

Peter W Atadja

{"title":"HDAC inhibitors and cancer therapy.","authors":"Peter W Atadja","doi":"10.1007/978-3-7643-8989-5_9","DOIUrl":"https://doi.org/10.1007/978-3-7643-8989-5_9","url":null,"abstract":"Maintenance of normal cell growth and differentiation is highly dependent on coordinated and tight transcriptional regulation of genes. In cancer, genes encoding growth regulators are abnormally expressed. Particularly, silencing of tumor suppressor genes under the control of chromatin modifications is a major underlying cause of unregulated cellular proliferation and transformation. Thus mechanisms, which regulate chromatin structure and gene expression, have become attractive targets for anticancer therapy. Histone deacetylases are enzymes that modify chromatin structure and contribute to aberrant gene expression in cancer. Research over the past decade has led to the development of histone deacetylase inhibitors as anticancer agents. In addition to their effect on chromatin and epigenetic mechanisms, HDAC inhibitors also modify the acetylation state of a large number of cellular proteins involved in oncogenic processes, resulting in antitumor effects. The current monograph will review the role of histone deacetylases in protumorigenic mechanisms and the current developmental status and prospects for their inhibitors in cancer therapy.","PeriodicalId":20603,"journal":{"name":"Progress in drug research. Fortschritte der Arzneimittelforschung. Progres des recherches pharmaceutiques","volume":"67 ","pages":"175-95"},"PeriodicalIF":0.0,"publicationDate":"2011-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/978-3-7643-8989-5_9","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29521327","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}

引用次数: 55

The liver-specific microRNA miR-122: biology and therapeutic potential. 肝脏特异性microRNA miR-122:生物学和治疗潜力。

Progress in drug research. Fortschritte der Arzneimittelforschung. Progres des recherches pharmaceutiques Pub Date : 2011-01-01

Witold Filipowicz, Helge Grosshans

引用次数: 0

Errors in erasure: links between histone lysine methylation removal and disease. 擦除错误:组蛋白赖氨酸甲基化去除与疾病之间的联系

Progress in drug research. Fortschritte der Arzneimittelforschung. Progres des recherches pharmaceutiques Pub Date : 2011-01-01 DOI: 10.1007/978-3-7643-8989-5_4

Elizabeth M Duncan, C David Allis

{"title":"Errors in erasure: links between histone lysine methylation removal and disease.","authors":"Elizabeth M Duncan, C David Allis","doi":"10.1007/978-3-7643-8989-5_4","DOIUrl":"https://doi.org/10.1007/978-3-7643-8989-5_4","url":null,"abstract":"Many studies have demonstrated that covalent histone modifications are dynamically regulated to cause both chemical and physical changes to the chromatin template. Such changes in the chromatin template lead to biologically significant consequences, including differential gene expression. Histone lysine methylation, in particular, has been shown to correlate with gene expression both positively and negatively, depending on the specific site and degree (i.e., mono-, di-, or tri-) of methylation within the histone sequence. Although genetic alterations in the proteins that establish, or \"write,\" methyl modifications and their effect in various human pathologies have been documented, connections between the misregulation of proteins that remove, or \"erase,\" histone methylation and disease have emerged more recently. Here we discuss three mechanisms through which histone methylation can be removed from the chromatin template. We describe how these \"erasure\" mechanisms are linked to pathways that are known to be misregulated in diseases, such as cancer. We further describe how errors in the removal of histone methylation can and do lead to human pathologies, both directly and indirectly.","PeriodicalId":20603,"journal":{"name":"Progress in drug research. Fortschritte der Arzneimittelforschung. Progres des recherches pharmaceutiques","volume":"67 ","pages":"69-90"},"PeriodicalIF":0.0,"publicationDate":"2011-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/978-3-7643-8989-5_4","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29521391","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}

引用次数: 24

Dynamics of histone lysine methylation: structures of methyl writers and erasers. 组蛋白赖氨酸甲基化动力学:甲基书写和甲基擦除的结构。

Progress in drug research. Fortschritte der Arzneimittelforschung. Progres des recherches pharmaceutiques Pub Date : 2011-01-01 DOI: 10.1007/978-3-7643-8989-5_6

Anup K Upadhyay, Xiaodong Cheng

引用次数: 60

Epigenetic mechanisms in acute myeloid leukemia. 急性髓性白血病的表观遗传机制。

Progress in drug research. Fortschritte der Arzneimittelforschung. Progres des recherches pharmaceutiques Pub Date : 2011-01-01 DOI: 10.1007/978-3-7643-8989-5_10

Antoine H F M Peters, Juerg Schwaller

{"title":"Epigenetic mechanisms in acute myeloid leukemia.","authors":"Antoine H F M Peters, Juerg Schwaller","doi":"10.1007/978-3-7643-8989-5_10","DOIUrl":"https://doi.org/10.1007/978-3-7643-8989-5_10","url":null,"abstract":"Acute leukemia is characterized by clonal expansion of hematopoietic stem and progenitor cells with blocked differentiation. Clinical and experimental evidences suggest that acute myeloid leukemia (AML) is the product of several functionally cooperating genetic alterations including chromosomal translocations leading to expression of leukemogenic fusion proteins. Several AML-associated lesions target chromatin regulators like histone methyltransferases or histone acetyltransferases, including mixed-lineage leukemia 1 (MLL1) or CREB bindung protein/p300. Molecular and biochemical studies start to provide useful insights into the mechanisms of targeting and mode-of-action of such leukemogenic fusion proteins resulting in aberrant gene expression programs and AML. Chromatin modulating mechanisms are also mediating the transforming activity of key drivers of leukemogenesis by aberrant recruitment of corepressors. Recent large-scale screening efforts demonstrated that both aberrant DNA promoter methylation and aberrantly expressed microRNAs play an important role in the pathogenesis of AML as well. Current efforts to therapeutically exploit the potential reversibility of epigenetic mechanisms are focused on small molecules that inhibit DNA methyltransferases or histone deacetylases. Several phase I/II clinical trials using such compounds have reported promising, but mostly transient, clinical responses. This underscores the need to further dissect the molecular players of epigenetic mechanisms driving induction, maintenance, and potential reversibility of leukemic state to develop efficient and long-lasting targeted therapeutic strategies.","PeriodicalId":20603,"journal":{"name":"Progress in drug research. Fortschritte der Arzneimittelforschung. Progres des recherches pharmaceutiques","volume":"67 ","pages":"197-219"},"PeriodicalIF":0.0,"publicationDate":"2011-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/978-3-7643-8989-5_10","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29521328","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}

引用次数: 10