Journal ArticleDOI
Clinical epigenetics: seizing opportunities for translation.
María Berdasco,Manel Esteller +1 more
TLDR
Beyond helping to understand disease biology, clinical epigenetics is being incorporated into patient management in oncology, as well as being explored for clinical applicability for other human pathologies such as neurological and infectious diseases and immune system disorders.Abstract:
Biomarker discovery and validation are necessary for improving the prediction of clinical outcomes and patient monitoring. Despite considerable interest in biomarker discovery and development, improvements in the range and quality of biomarkers are still needed. The main challenge is how to integrate preclinical data to obtain a reliable biomarker that can be measured with acceptable costs in routine clinical practice. Epigenetic alterations are already being incorporated as valuable candidates in the biomarker field. Furthermore, their reversible nature offers a promising opportunity to ameliorate disease symptoms by using epigenetic-based therapy. Thus, beyond helping to understand disease biology, clinical epigenetics is being incorporated into patient management in oncology, as well as being explored for clinical applicability for other human pathologies such as neurological and infectious diseases and immune system disorders.read more
Citations
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Journal ArticleDOI
The Unexpected Noncatalytic Roles of Histone Modifiers in Development and Disease.
TL;DR: An overview of surprising, yet exciting, noncanonical, noncatalytic roles uncovered in transcriptional regulation for histone modifying enzymes and how these revelations may have important implications for understanding disease and the future of epigenome-targeting therapies are highlighted.
Journal ArticleDOI
The histone methyltransferase DOT1L prevents antigen-independent differentiation and safeguards epigenetic identity of CD8+ T cells
Eliza Mari Kwesi-Maliepaard,Muhammad Aslam,Muhammad Aslam,Mir Farshid Alemdehy,Teun van den Brand,Chelsea M. McLean,Hanneke Vlaming,Tibor van Welsem,Tessy Korthout,Cesare Lancini,Sjoerd Hendriks,Tomasz Ahrends,Dieke van Dinther,Joke M. M. den Haan,Jannie Borst,Elzo de Wit,Fred van Leeuwen,Fred van Leeuwen,Heinz Jacobs +18 more
TL;DR: It is shown that the histone methyltransferase DOT1L, which marks the nucleosome core on active genes, safeguards normal differentiation of CD8+ T cells and acts as a barrier to prevent premature differentiation and controlling epigenetic integrity.
Journal ArticleDOI
From fiction to science: clinical potentials and regulatory considerations of gene editing
Maria Schacker,Diane Seimetz +1 more
TL;DR: How gene editing technologies are altering the gene therapy landscape is discussed and the regulatory challenges associated with such therapies and how they can be tackled during the drug development process are discussed.
Journal ArticleDOI
Epigenetics in hepatocellular carcinoma
TL;DR: In this article , the authors have summarized the epigenetic modifications involved in HCC progression and highlighted the potential biomarkers for diagnosis and drug development, which can provide a meaningful improvement in overall survival and prediction of therapeutic outcomes.
Journal ArticleDOI
Leveraging clinical epigenetics in heart failure with preserved ejection fraction: a call for individualized therapies.
Nazha Hamdani,Sarah Costantino,Andreas Mügge,Djamel Lebeche,Carsten Tschöpe,Thomas Thum,Thomas Thum,Francesco Paneni +7 more
TL;DR: In this article, the authors discuss the importance of clinical epigenetics as a new tool to be employed for a personalized management of heart failure with preserved ejection fraction (HFpEF).
References
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Journal ArticleDOI
Integrative analysis of 111 reference human epigenomes
Anshul Kundaje,Wouter Meuleman,Wouter Meuleman,Jason Ernst,Misha Bilenky,Angela Yen,Angela Yen,Alireza Heravi-Moussavi,Pouya Kheradpour,Pouya Kheradpour,Zhizhuo Zhang,Zhizhuo Zhang,Jianrong Wang,Jianrong Wang,Michael J. Ziller,Viren Amin,John W. Whitaker,Matthew D. Schultz,Lucas D. Ward,Lucas D. Ward,Abhishek Sarkar,Abhishek Sarkar,Gerald Quon,Gerald Quon,Richard Sandstrom,Matthew L. Eaton,Matthew L. Eaton,Yi-Chieh Wu,Yi-Chieh Wu,Andreas R. Pfenning,Andreas R. Pfenning,Xinchen Wang,Xinchen Wang,Melina Claussnitzer,Melina Claussnitzer,Yaping Liu,Yaping Liu,Cristian Coarfa,R. Alan Harris,Noam Shoresh,Charles B. Epstein,Elizabeta Gjoneska,Elizabeta Gjoneska,Danny Leung,Wei Xie,R. David Hawkins,Ryan Lister,Chibo Hong,Philippe Gascard,Andrew J. Mungall,Richard A. Moore,Eric Chuah,Angela Tam,Theresa K. Canfield,R. Scott Hansen,Rajinder Kaul,Peter J. Sabo,Mukul S. Bansal,Mukul S. Bansal,Mukul S. Bansal,Annaick Carles,Jesse R. Dixon,Kai How Farh,Soheil Feizi,Soheil Feizi,Rosa Karlic,Ah Ram Kim,Ah Ram Kim,Ashwinikumar Kulkarni,Daofeng Li,Rebecca F. Lowdon,Ginell Elliott,Tim R. Mercer,Shane Neph,Vitor Onuchic,Paz Polak,Paz Polak,Nisha Rajagopal,Pradipta R. Ray,Richard C Sallari,Richard C Sallari,Kyle Siebenthall,Nicholas A Sinnott-Armstrong,Nicholas A Sinnott-Armstrong,Michael Stevens,Robert E. Thurman,Jie Wu,Bo Zhang,Xin Zhou,Arthur E. Beaudet,Laurie A. Boyer,Philip L. De Jager,Philip L. De Jager,Peggy J. Farnham,Susan J. Fisher,David Haussler,Steven J.M. Jones,Steven J.M. Jones,Wei Li,Marco A. Marra,Michael T. McManus,Shamil R. Sunyaev,Shamil R. Sunyaev,James A. Thomson,Thea D. Tlsty,Li-Huei Tsai,Li-Huei Tsai,Wei Wang,Robert A. Waterland,Michael Q. Zhang,Lisa Helbling Chadwick,Bradley E. Bernstein,Bradley E. Bernstein,Bradley E. Bernstein,Joseph F. Costello,Joseph R. Ecker,Martin Hirst,Alexander Meissner,Aleksandar Milosavljevic,Bing Ren,John A. Stamatoyannopoulos,Ting Wang,Manolis Kellis,Manolis Kellis +123 more
TL;DR: It is shown that disease- and trait-associated genetic variants are enriched in tissue-specific epigenomic marks, revealing biologically relevant cell types for diverse human traits, and providing a resource for interpreting the molecular basis of human disease.
Integrative analysis of 111 reference human epigenomes
Anshul Kundaje,Wouter Meuleman,Jason Ernst,Angela Yen,Pouya Kheradpour,Zhizhuo Zhang,Jianrong Wang,Lucas D. Ward,Abhishek Sarkar,Gerald Quon,Matthew L. Eaton,Yi-Chieh Wu,Andreas R. Pfenning,Xinchen Wang,Melina Claussnitzer,Yaping Liu,Mukul S. Bansal,Soheil Feizi-Khankandi,Ah Ram Kim,Richard C Sallari,Nicholas A Sinnott-Armstrong,Laurie A. Boyer,Elizabeta Gjoneska,Li-Huei Tsai,Manolis Kellis +24 more
TL;DR: In this article, the authors describe the integrative analysis of 111 reference human epigenomes generated as part of the NIH Roadmap Epigenomics Consortium, profiled for histone modification patterns, DNA accessibility, DNA methylation and RNA expression.
Journal ArticleDOI
Non-coding RNAs in human disease
TL;DR: Dysregulation of these ncRNAs is being found to have relevance not only to tumorigenesis, but also to neurological, cardiovascular, developmental and other diseases, and there is great interest in therapeutic strategies to counteract these perturbations.