Enhancers in disease: molecular basis and emerging treatment strategies.
TLDR
In this article, the authors review how these enhancer disruptions have recently been implicated in congenital disorders, cancers, and common complex diseases and address the implications for diagnosis and treatment, and show that enhancer-targeting drugs and gene editing approaches show great therapeutic promise for a range of diseases.About:
This article is published in Trends in Molecular Medicine.The article was published on 2021-11-01 and is currently open access. It has received 39 citations till now. The article focuses on the topics: Enhancer.read more
Citations
More filters
Journal ArticleDOI
Toward transcriptomics as a primary tool for rare disease investigation
TL;DR: It is speculated that as advances in computational methods and emerging experimental techniques overcome both developmental and cell type specificity, there will be broadening use of RNA sequencing and multiomics in rare disease diagnosis and delivery of precision health.
Journal ArticleDOI
Translating osteoarthritis genetics research: challenging times ahead
TL;DR: In this paper , the potential for OA genetic data to translate is discussed, including whether the developmental origin of OA will limit the application of genetic risk data for disease-modification purposes.
Journal ArticleDOI
Current challenges in understanding the role of enhancers in disease.
Judith B. Zaugg,Pelin Sahlén,Robin Andersson,Meritxell Alberich-Jorda,Wouter de Laat,Bart Deplancke,Jorge Ferrer,Susanne Mandrup,Gioacchino Natoli,Dariusz Plewczynski,Alvaro Rada-Iglesias,Salvatore Spicuglia +11 more
TL;DR: The role of enhancers in disease etiology and highlighting opportunities and directions for future studies, aiming to disentangle the molecular basis of enhanceropathies is discussed in this paper .
Journal ArticleDOI
Enhancer-gene specificity in development and disease.
TL;DR: Recent insights into the factors controlling enhancer specificity are discussed, including the genetic composition of enhancer and promoters, the linear and 3D distance between enhancers and their target genes, and cell-type specific chromatin landscapes.
Journal ArticleDOI
Multiscale 3D genome organization underlies ILC2 ontogenesis and allergic airway inflammation
Michaël F. Michieletto,John Tello-Cajiao,Walter K. Mowel,Aditi Chandra,So-Yoon Yoon,Leonel Joannas,Megan L. Clark,Monica T. Jimenez,Jasmine M. Wright,Patrick Lundgren,Adam Williams,Christoph A. Thaiss,Golnaz Vahedi,Jorge Henao-Mejia +13 more
TL;DR: Henao-Mejia et al. as mentioned in this paper carried out an integrative analysis of the 3D genome structure, chromatin accessibility and gene expression in mature ILCs and revealed that the local 3D configuration of the genome is rewired specifically at loci associated with ILC biology to promote their development and functional differentiation.
References
More filters
Journal ArticleDOI
A 3D Map of the Human Genome at Kilobase Resolution Reveals Principles of Chromatin Looping
Suhas S.P. Rao,Miriam H. Huntley,Neva C. Durand,Elena K. Stamenova,Ivan D. Bochkov,James T. Robinson,James T. Robinson,Adrian L. Sanborn,Ido Machol,Ido Machol,Arina D. Omer,Arina D. Omer,Eric S. Lander,Eric S. Lander,Eric S. Lander,Erez Lieberman Aiden +15 more
TL;DR: In situ Hi-C is used to probe the 3D architecture of genomes, constructing haploid and diploid maps of nine cell types, identifying ∼10,000 loops that frequently link promoters and enhancers, correlate with gene activation, and show conservation across cell types and species.
Journal ArticleDOI
Topological domains in mammalian genomes identified by analysis of chromatin interactions
Jesse R. Dixon,Siddarth Selvaraj,Siddarth Selvaraj,Feng Yue,Audrey Kim,Yan-Yan Li,Yin-Zhong Shen,Ming Hu,Jun Liu,Bing Ren,Bing Ren +10 more
TL;DR: It is found that the boundaries of topological domains are enriched for the insulator binding protein CTCF, housekeeping genes, transfer RNAs and short interspersed element (SINE) retrotransposons, indicating that these factors may have a role in establishing the topological domain structure of the genome.
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.
Journal ArticleDOI
Systematic localization of common disease-associated variation in regulatory DNA.
Matthew T. Maurano,Richard Humbert,Eric Rynes,Robert E. Thurman,Eric Haugen,Hao Wang,Alex Reynolds,Richard Sandstrom,Hongzhu Qu,Hongzhu Qu,Jennifer A. Brody,Anthony Shafer,Fidencio Neri,Kristen Lee,Tanya Kutyavin,Sandra Stehling-Sun,Audra K. Johnson,Theresa K. Canfield,Erika Giste,Morgan Diegel,Daniel Bates,R. Scott Hansen,Shane Neph,Peter J. Sabo,Shelly Heimfeld,Antony Raubitschek,Steven F. Ziegler,Chris Cotsapas,Nona Sotoodehnia,Ian A. Glass,Shamil R. Sunyaev,Rajinder Kaul,John A. Stamatoyannopoulos +32 more
TL;DR: P pervasive involvement of regulatory DNA variation in common human disease and provide pathogenic insights into diverse disorders are suggested.
Journal ArticleDOI
Spatial partitioning of the regulatory landscape of the X-inactivation centre
Elphège P. Nora,Bryan R. Lajoie,Edda G. Schulz,Luca Giorgetti,Luca Giorgetti,Luca Giorgetti,Ikuhiro Okamoto,Ikuhiro Okamoto,Ikuhiro Okamoto,Nicolas Servant,Nicolas Servant,Nicolas Servant,Tristan Piolot,Tristan Piolot,Tristan Piolot,Nynke L. van Berkum,Johannes Meisig,John W. Sedat,Joost Gribnau,Emmanuel Barillot,Emmanuel Barillot,Emmanuel Barillot,Nils Blüthgen,Job Dekker,Edith Heard,Edith Heard,Edith Heard +26 more
TL;DR: In addition to uncovering a new principle of cis-regulatory architecture of mammalian chromosomes, this study sets the stage for the full genetic dissection of the mouse X-inactivation centre.