Epigenetic Technological Applications PDF
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Epigenetic Technological Applications Epigenetic Technological Applications Edited by Y. George Zheng AMSTERDAM(cid:129)BOSTON(cid:129)HEIDELBERG(cid:129)LONDON NEWYORK(cid:129)OXFORD(cid:129)PARIS(cid:129)SANDIEGO SANFRANCISCO(cid:129)SINGAPORE(cid:129)SYDNEY(cid:129)TOKYO AcademicPressisanimprintofElsevier AcademicPressisanimprintofElsevier 125,LondonWall,EC2Y5AS 525BStreet,Suite1800,SanDiego,CA92101-4495,USA 225WymanStreet,Waltham,MA02451,USA TheBoulevard,LangfordLane,Kidlington,OxfordOX51GB,UK Copyrightr2015ElsevierInc.Allrightsreserved. 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LibraryofCongressCataloging-in-PublicationData AcatalogrecordforthisbookisavailablefromtheLibraryofCongress BritishLibraryCataloguing-in-PublicationData AcataloguerecordforthisbookisavailablefromtheBritishLibrary ISBN:978-0-12-801080-8 Forinformationonallpublicationsvisit ourwebsiteathttp://store.elsevier.com TypesetbyMPSLimited,Chennai,India www.adi-mps.com Publisher:MicaHaley AcquisitionEditor:CatherineVanDerLaan EditorialProjectManager:LisaEppich ProductionProjectManager:MelissaRead Designer:AlanStudholme PrintedandboundintheUnitedStatesofAmerica List of Contributors Alison I. Bernstein Department ofHuman Genetics, Emory University,Atlanta, GA, USA Kelly M. Biette Massachusetts General Hospital Cancer Center and Department of Medicine, Harvard Medical School,Charlestown, MA, USA JoshuaC. Black Massachusetts General Hospital Cancer Center and Department of Medicine, Harvard Medical School,Charlestown, MA, USA Champak Chatterjee Department ofChemistry,University ofWashington, Seattle,WA,USA AiliChen Divisions of Experimental Hematology and Cancer Biology, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio, USA; Division of Pathology, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio, USA; Key Laboratory of Genomic and Precision Medicine, Beijing Institute ofGenomics, Chinese Academy of Sciences, Beijing, China XiangyunAmy Chen Center for Eukaryotic Gene Regulation, Department of Biochemistry and Molecular Biology, PennsylvaniaStateUniversity,PA,USA AbhinavDhall Department ofChemistry,University ofWashington, Seattle,WA,USA Alfonso Duen˜as-Gonza´lez Instituto de Investigaciones Biome´dicas, Universidad Nacional Auto´noma de Me´xico and Unidadde Investigacio´nBiome´dica en Ca´ncer,InstitutoNacional deCancerologı´a,Me´xico Yuhong Fan School of Biology, Georgia Institute of Technology, Atlanta, GA, USA; The Petit Institute for Bioengineering and Bioscience, Georgia Instituteof Technology,Atlanta, GA, USA Benjamin A.Garcia Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania,Philadelphia, PA,USA Zhen Han Department of Pharmaceutical and Biochemical Sciences, The University of Georgia, Athens, Georgia,USA Alexander-ThomasHauser Institute ofPharmaceutical Sciences, Albert-Ludwigs-University ofFreiburg, Germany xvii xviii List of Contributors GangHuang Divisions ofExperimental Hematology and Cancer Biology,Cincinnati Children’sHospital Medical Center,Cincinnati, Ohio,USA; Division ofPathology, CincinnatiChildren’s Hospital Medical Center,Cincinnati, Ohio,USA Kenneth Huang Department of Chemistry, Georgia State University,Atlanta,GA, USA PengJin Department of Human Genetics, EmoryUniversity,Atlanta,GA, USA Manfred Jung InstituteofPharmaceuticalSciences, Albert-Ludwigs-University ofFreiburg, Germany Shukkoor Kondengaden Department of Chemistry, Georgia State University,Atlanta,GA, USA JamesR. Kornacki DepartmentsofChemistryandBiomedicalEngineering,NorthwesternUniversity,Evanston,IL,USA HaitaoLi Department of Basic Medical Sciences, Center for StructuralBiology, School of Medicine, Tsinghua University, Beijing, P.R. China KeqinKathy Li Department of Chemistry, Georgia State University,Atlanta,GA, USA; State KeyLab of Medical Genomic, Ruijin Hospital Affiliated toMedical School ofShanghai Jiaotong University,Shanghai, P.R. China Junyan Lu DrugDiscovery and Design Center,StateKeyLaboratory ofDrugResearch, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai,China YepengLuan Department of Pharmaceutical and Biochemical Sciences, The University ofGeorgia,Athens, Georgia, USA ChengLuo DrugDiscovery and Design Center,StateKeyLaboratory ofDrugResearch, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai,China MinkuiLuo Molecular Pharmacology and Chemistry Program, Memorial Sloan KetteringCancerCenter, New York, NY,USA AntoniaMasch Department of Enzymology,Institute ofBiochemistry & Biotechnology,Martin-Luther-University Halle-Wittenberg,Halle,Germany Jose´ L. Medina-Franco Facultad de Qu´ımica, Departamento de Farmacia,Universidad Nacional Auto´noma de Me´xico, MexicoCity,Mexico List of Contributors xix Milan Mrksich Departments of Chemistry and Biomedical Engineering, Northwestern University, Evanston, IL, USA Liza Ngo Department of Pharmaceutical and Biochemical Sciences, The University of Georgia, Athens, Georgia,USA Adegboyega K. Oyelere Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA, USA; School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, GA, USA Chenyi Pan School of Biology, Georgia Institute of Technology, Atlanta, GA, USA; The Petit Institute for Bioengineering and Bioscience, Georgia Instituteof Technology,Atlanta, GA, USA Sriharsa Pradhan GenomeBiologyDivision,New England Biolabs, Ipswich,Massachusetts, USA Zhang Qing Department ofChemistry,Georgia State University,Atlanta, GA, USA Meihua Qu College of Pharmaceutical and Biological Sciences, Weifang Medical University, Weifang, Shandong,P.R. China Ulf Reimer JPT PeptideTechnologies GmbH,Berlin,Germany Hamed Reyhanfard Department ofChemistry,Georgia State University,Atlanta, GA, USA Martin Roatsch Institute ofPharmaceutical Sciences, Albert-Ludwigs-University ofFreiburg, Germany Dina Robaa Department of Pharmaceutical Chemistry, Martin Luther University of Halle-Wittenberg, Germany JohannesSchulz-Fincke German Cancer Consortium, Heidelberg, Germany; German Cancer Research Center, Heidelberg, Germany; Institute of Pharmaceutical Sciences, Albert-Ludwigs-University of Freiburg, Germany Mike Schutkowski Department of Enzymology, Institute of Biochemistry & Biotechnology, Martin-Luther-University Halle-Wittenberg,Halle,Germany Simone Sidoli Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania,Philadelphia, PA,USA xx List of Contributors Wolfgang Sippl Department of Pharmaceutical Chemistry,Martin Luther University of Halle-Wittenberg, Germany Quaovi H.Sodji School ofChemistry and Biochemistry, Georgia Institute ofTechnology,Atlanta, GA, USA JinquanSun Center for Eukaryotic Gene Regulation, Department ofBiochemistry and Molecular Biology, Pennsylvania State University, PA, USA JolyonTerragni GenomeBiology Division, New England Biolabs, Ipswich,Massachusetts,USA Xiao-JunTian Department of Computational and Systems Biology,School ofMedicine,University of Pittsburgh, Pittsburgh,PA, USA PengGeorgeWang Department of Chemistry, Georgia State University,Atlanta,GA, USA XiaoshiWang Department of Biochemistry and Biophysics, Perelman School ofMedicine,University of Pennsylvania,Philadelphia, PA, USA XuejianWang Collegeof Pharmaceutical and Biological Sciences, WeifangMedical University, Weifang, Shandong, P.R. China YanmingWang Center for Eukaryotic Gene Regulation, Department ofBiochemistry and Molecular Biology, Pennsylvania State University, PA, USA Johnathan R.Whetstine Massachusetts General Hospital CancerCenter and Department ofMedicine, Harvard Medical School, Charlestown, MA, USA JonathanWooten Department of Chemistry, Georgia State University,Atlanta,GA, USA JianhuaXing BeijingComputationalScience Research Center, Beijing, China; Department ofComputational and Systems Biology,School ofMedicine, University ofPittsburgh,Pittsburgh, PA, USA Wei Xu McArdleLaboratory for CancerResearch, University ofWisconsin-Madison,Madison, WI,USA Jakyung Yoo Life Science Research Institute,Daewoong Pharmaceutical Co.,Ltd, Gyeonggi-do, Republic of Korea List of Contributors xxi Jin Yu Beijing Computational Science ResearchCenter,Beijing, China Hao Zeng McArdleLaboratory for Cancer Research,University ofWisconsin-Madison,Madison, WI,USA JohannesZerweck JPT PeptideTechnologies GmbH,Berlin,Germany BingxueChrisZhai Department ofBiology,Georgia State University, Atlanta, GA, USA Hang Zhang Beijing Computational Science Research Center, Beijing, China; Department of Biological Sciences, Virginia PolytechnicInstitute and StateUniversity,Blacksburg, VA,USA Hao Zhang Drug Discovery and Design Center, State Key Laboratory of Drug Research, Shanghai Institute ofMateria Medica, Chinese Academy ofSciences, Shanghai, China Liyi Zhang Drug Discovery and Design Center, State Key Laboratory of Drug Research, Shanghai Institute ofMateria Medica, Chinese Academy ofSciences, Shanghai, China Yunzhe Zhang School of Biology, Georgia Institute of Technology, Atlanta, GA, USA; The Petit Institute for Bioengineering and Bioscience, Georgia Instituteof Technology,Atlanta, GA, USA Shuai Zhao Department of Basic Medical Sciences, Center for Structural Biology, School of Medicine, Tsinghua University,Beijing, P.R. China Y.GeorgeZheng Department of Pharmaceutical and Biochemical Sciences, The University of Georgia, Athens, Georgia,USA Foreword Epigenetics refers to heritable differences in phenotype that cannot be attributed to differences in DNA sequence. Epigenetics is emerging as a cornerstone of modern biology with important and promising practical implications for current and future therapeutics. Over the past 15 years we have come to recognize that patterns of chemical modifications on chromatin (cid:1) on both proteins and DNA (cid:1) establish heritable and dynamic gene expression programsresponsible for cell type identity through development, adaptation to environmental conditions, and evolution and maintenance of disease states. Our ability to translate this growing body of knowledge into useful strategies to understand, diagnose and treat human disease depends critically on the development and applica- tion of technologies to characterize and manipulate the “epigenetic state” of normal and diseased cells and to correlate those states with phenotype. This book summarizes many of these key tech- nologies with emphasis on epigenetic regulation mediated by methylation and acetylation (cid:1) the two most abundant anddiverse epigenetic “marks.” Much progress has been made in recent years in identifying and characterizing the protein fac- tors that “write,” “read” and “erase” methyl and acetyl marks using methodologies ranging from cell and molecular biology, genomics and bioinformatics, structural biology, protein biochemistry and enzymology. These studies have described the major protein families and complexes that inter- act with and modify chromatin and have revealed many of them to be “druggable.” Indeed, the dis- covery of novel inhibitors of histone deacetylases and DNA hypomethylation agents with clinical benefits in oncology has spurred the continued development of new drugs and chemical tools for epigenetics research and therapy. However, there remains a significant gap in our understanding of the patterns of methylation and acetylation that define both normal and diseased epigenetic states. Recent large-scale projects (such as the Encode Project) to catalogue the localization of epigenetic marks along the genome in different common cell lines have provided a good starting point, but the community now needs to better understand how these patterns differ in human disease and how they can be selectively manipulated for safe therapies. The use and further development of genome- and proteome-wide technologies that can map the locations of epigenetic marks along the genome are particularly powerful in this regard. Further optimization and more widespread application of these “omics” technologies todisease tissue will be essential tothe fullrealization of new epigenetic therapies. The following survey of epigenetic technologies will serve as an important benchmark for our current capabilities and will inspire further technological advances to reduce the knowledge gap and facilitate more rapid and successful translation of epigenetics research into new diagnoses and therapies. Cheryl H.Arrowsmith University ofToronto xxiii CHAPTER 1 THE STATE OF THE ART OF EPIGENETIC TECHNOLOGIES Y. George Zheng DepartmentofPharmaceuticalandBiochemicalSciences, TheUniversityofGeorgia,Athens,Georgia,USA CHAPTER OUTLINE 1.1 EpigeneticsandChromatinFunction...................................................................................................1 1.2 MechanismsofEpigeneticRegulation................................................................................................2 1.3 TechnologiesAreCriticalfortheAdvancementofEpigeneticDiscovery...............................................8 1.4 EpigeneticInhibitorsasNovelTherapeutics....................................................................................11 1.5 Perspective...................................................................................................................................12 Acknowledgments.................................................................................................................................14 References...........................................................................................................................................14 1.1 EPIGENETICS AND CHROMATIN FUNCTION The field of epigenetics is rapidly booming, evolving, and expanding. The term epigenetics (the prefix “epi” comes from Greek, meaning over, upon, above, in addition to) was created by Waddington in the context of connecting developmental biology and genetics [1]. To date, epige- netics is most frequently referred to as the study of meiotically and mitotically heritable changes in gene activities without alterations in the genetic DNA sequence [1(cid:1)4]. However, in recent years, it has been debated whether the heritability requirement of the term is necessary or too restrictive given that many (perhaps most) changes in gene activity modulated by chromatin modifications can occur in terminally differentiated and nondividing cells [3,5,6]. Examples include short-lived alterations in histone acetylation and methylation caused by DNA repair, cell-cycle phase, or tran- scription factor binding. Thus, there exist arguments in which epigenetic changes could be more broadly defined to encompass structural and biochemical alterations of the chromatin at any point in time under the condition that the genetic sequence is kept invariable [5,6]. Under this scheme, epigenetics does not merely refer to heritable chromatin states, but also embraces those that are transient or occur in nondividing cells. A new term, memigenetics, has recently been suggested to Y.G.Zheng(Ed):EpigeneticTechnologicalApplications.DOI:http://dx.doi.org/10.1016/B978-0-12-801080-8.00001-6 1 ©2015ElsevierInc.Allrightsreserved.
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