Constitutive nuclear lamina–genome interactions are highly conserved and associated with A/T-rich sequence
Wouter Meuleman,Daan Peric-Hupkes,Jop Kind,Jean-Bernard Beaudry,Ludo Pagie,Manolis Kellis,Manolis Kellis,Marcel J. T. Reinders,Lodewyk F. A. Wessels,Lodewyk F. A. Wessels,Bas van Steensel +10 more
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TLDR
Results reveal that the spatial organization of mammalian genomes is highly conserved and tightly linked to local nucleotide composition.Abstract:
In metazoans, the nuclear lamina is thought to play an important role in the spatial organization of interphase chromosomes, by providing anchoring sites for large genomic segments named lamina-associated domains (LADs). Some of these LADs are cell-type specific, while many others appear constitutively associated with the lamina. Constitutive LADs (cLADs) may contribute to a basal chromosome architecture. By comparison of mouse and human lamina interaction maps, we find that the sizes and genomic positions of cLADs are strongly conserved. Moreover, cLADs are depleted of synteny breakpoints, pointing to evolutionary selective pressure to keep cLADs intact. Paradoxically, the overall sequence conservation is low for cLADs. Instead, cLADs are universally characterized by long stretches of DNA of high A/T content. Cell-type specific LADs also tend to adhere to this "A/T rule" in embryonic stem cells, but not in differentiated cells. This suggests that the A/T rule represents a default positioning mechanism that is locally overruled during lineage commitment. Analysis of paralogs suggests that during evolution changes in A/T content have driven the relocation of genes to and from the nuclear lamina, in tight association with changes in expression level. Taken together, these results reveal that the spatial organization of mammalian genomes is highly conserved and tightly linked to local nucleotide composition.read more
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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
Nuclear lamin-A Scales With Tissue Stiffness and Enhances Matrix-Directed Differentiation
Joe Swift,Irena L. Ivanovska,Amnon Buxboim,Takamasa Harada,P.C. Dave P. Dingal,Joel Pinter,J. David Pajerowski,Kyle R. Spinler,Jae-Won Shin,Manorama Tewari,Florian Rehfeldt,David W. Speicher,Dennis E. Discher,Dennis E. Discher +13 more
TL;DR: In this article, proteomics analyses revealed that levels of the nucleoskeletal protein lamin-A scaled with tissue elasticity, as did levels of collagens in the extracellular matrix that determine E.
Journal ArticleDOI
Two independent modes of chromatin organization revealed by cohesin removal
Wibke Schwarzer,Nezar Abdennur,Anton Goloborodko,Aleksandra Pekowska,Geoffrey Fudenberg,Yann Loe-Mie,Nuno A. Fonseca,Wolfgang Huber,Christian H. Haering,Leonid A. Mirny,François Spitz +10 more
TL;DR: It is shown that deletion of the cohesin-loading factor Nipbl in mouse liver leads to a marked reorganization of chromosomal folding, and the disappearance of TADs unmasks a finer compartment structure that accurately reflects the underlying epigenetic landscape.
Journal ArticleDOI
Topologically associating domains are stable units of replication-timing regulation
Benjamin D. Pope,Tyrone Ryba,Vishnu Dileep,Feng Yue,Weisheng Wu,Olgert Denas,Daniel L. Vera,Yanli Wang,R. Scott Hansen,Theresa K. Canfield,Robert E. Thurman,Yong Cheng,Günhan Gülsoy,Jonathan H. Dennis,Michael Snyder,John A. Stamatoyannopoulos,James Taylor,Ross C. Hardison,Tamer Kahveci,Bing Ren,David M. Gilbert +20 more
TL;DR: It is demonstrated that, collectively, replication domain boundaries share a near one-to-one correlation with TAD boundaries, whereas within a cell type, adjacent TADs that replicate at similar times obscure replicationdomain boundaries, largely accounting for the previously reported lack of alignment.
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