Journal ArticleDOI
Transposable elements have rewired the core regulatory network of human embryonic stem cells
Galih Kunarso,Na-Yu Chia,Na-Yu Chia,Justin Jeyakani,Catalina Hwang,Catalina Hwang,Xinyi Lu,Xinyi Lu,Yun-Shen Chan,Yun-Shen Chan,Huck-Hui Ng,Guillaume Bourque +11 more
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It is shown that species-specific transposable elements have substantially altered the transcriptional circuitry of pluripotent stem cells and have wired new genes into the core regulatory network of embryonic stem cells.Abstract:
Detection of new genomic control elements is critical in understanding transcriptional regulatory networks in their entirety. We studied the genome-wide binding locations of three key regulatory proteins (POU5F1, also known as OCT4; NANOG; and CTCF) in human and mouse embryonic stem cells. In contrast to CTCF, we found that the binding profiles of OCT4 and NANOG are markedly different, with only approximately 5% of the regions being homologously occupied. We show that transposable elements contributed up to 25% of the bound sites in humans and mice and have wired new genes into the core regulatory network of embryonic stem cells. These data indicate that species-specific transposable elements have substantially altered the transcriptional circuitry of pluripotent stem cells.read more
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Mapping and analysis of chromatin state dynamics in nine human cell types
Jason Ernst,Pouya Kheradpour,Pouya Kheradpour,Tarjei S. Mikkelsen,Noam Shoresh,Lucas D. Ward,Lucas D. Ward,Charles B. Epstein,Xiaolan Zhang,Li Wang,Robbyn Issner,Michael Coyne,Manching Ku,Manching Ku,Manching Ku,Timothy Durham,Manolis Kellis,Manolis Kellis,Bradley E. Bernstein,Bradley E. Bernstein,Bradley E. Bernstein +20 more
TL;DR: This study presents a general framework for deciphering cis-regulatory connections and their roles in disease, and maps nine chromatin marks across nine cell types to systematically characterize regulatory elements, their cell-type specificities and their functional interactions.
Journal ArticleDOI
lincRNAs act in the circuitry controlling pluripotency and differentiation
Mitchell Guttman,Julie Donaghey,Bryce W. Carey,Manuel Garber,Jennifer K. Grenier,Glen Munson,Geneva Young,Anne Bergstrom Lucas,Robert A. Ach,Laurakay Bruhn,Xiaoping Yang,Ido Amit,Alexander Meissner,Alexander Meissner,Aviv Regev,Aviv Regev,John L. Rinn,John L. Rinn,David E. Root,Eric S. Lander,Eric S. Lander,Eric S. Lander +21 more
TL;DR: It is shown that Knockdown of lincRNAs has major consequences on gene expression patterns, comparable to knockdown of well-known ES cell regulators.
Journal Article
Mapping and Analysis of Chromatin State Dynamics in Nine Human Cell Types
Jason Ernst,Pouya Kheradpour,Pouya Kheradpour,Tarjei S. Mikkelsen,Noam Shoresh,Lucas D. Ward,Lucas D. Ward,Charles B. Epstein,Xiaolan Zhang,Li Wang,Robbyn Issner,Michael Coyne,Manching Ku,Manching Ku,Manching Ku,Timothy Durham,Manolis Kellis,Manolis Kellis,Bradley E. Bernstein,Bradley E. Bernstein,Bradley E. Bernstein +20 more
TL;DR: This study presents a general framework for deciphering cis-regulatory connections and their roles in disease, and defines multi-cell activity profiles for chromatin state, gene expression, regulatory motif enrichment, and regulator expression.
Journal ArticleDOI
A comparative encyclopedia of DNA elements in the mouse genome
Feng Yue,Feng Yue,Yong Cheng,Alessandra Breschi,Jeff Vierstra,Weisheng Wu,Weisheng Wu,Tyrone Ryba,Tyrone Ryba,Richard Sandstrom,Zhihai Ma,Carrie A. Davis,Benjamin D. Pope,Yin Shen,Dmitri D. Pervouchine,Sarah Djebali,Robert E. Thurman,Rajinder Kaul,Eric Rynes,Anthony Kirilusha,Georgi K. Marinov,Brian A. Williams,Diane Trout,Henry Amrhein,Katherine I. Fisher-Aylor,Igor Antoshechkin,Gilberto DeSalvo,Lei Hoon See,Meagan Fastuca,Jorg Drenkow,Chris Zaleski,Alexander Dobin,Pablo Prieto,Julien Lagarde,Giovanni Bussotti,Andrea Tanzer,Olgert Denas,Kanwei Li,M. A. Bender,M. A. Bender,Miaohua Zhang,Rachel Byron,Mark Groudine,Mark Groudine,David McCleary,Long Pham,Zhen Ye,Samantha Kuan,Lee Edsall,Yi-Chieh Wu,Matthew D. Rasmussen,Mukul S. Bansal,Manolis Kellis,Manolis Kellis,Cheryl A. Keller,Christapher S. Morrissey,Tejaswini Mishra,Deepti Jain,Nergiz Dogan,Robert S. Harris,Philip Cayting,Trupti Kawli,Alan P. Boyle,Alan P. Boyle,Ghia Euskirchen,Anshul Kundaje,Shin Lin,Yiing Lin,Camden Jansen,Venkat S. Malladi,Melissa S. Cline,Drew T. Erickson,Vanessa M. Kirkup,Katrina Learned,Cricket A. Sloan,Kate R. Rosenbloom,Beatriz Lacerda de Sousa,Kathryn Beal,Miguel Pignatelli,Paul Flicek,Jin Lian,Tamer Kahveci,Dongwon Lee,W. James Kent,Miguel Santos,Javier Herrero,Cedric Notredame,Audra K. Johnson,Shinny Vong,Kristen Lee,Daniel Bates,Fidencio Neri,Morgan Diegel,Theresa K. Canfield,Peter J. Sabo,Matthew S. Wilken,Thomas A. Reh,Erika Giste,Anthony Shafer,Tanya Kutyavin,Eric Haugen,Douglas Dunn,Alex Reynolds,Shane Neph,Richard Humbert,R. Scott Hansen,Marella F. T. R. de Bruijn,Licia Selleri,Alexander Y. Rudensky,Steven Z. Josefowicz,Robert M. Samstein,Evan E. Eichler,Stuart H. Orkin,Dana N. Levasseur,Thalia Papayannopoulou,Kai Hsin Chang,Arthur I. Skoultchi,Srikanta Gosh,Christine M. Disteche,Piper M. Treuting,Yanli Wang,Mitchell J. Weiss,Gerd A. Blobel,Xiaoyi Cao,Sheng Zhong,Ting Wang,Peter J. Good,Rebecca F. Lowdon,Rebecca F. Lowdon,Leslie B. Adams,Leslie B. Adams,Xiao Qiao Zhou,Michael J. Pazin,Elise A. Feingold,Barbara J. Wold,James Taylor,Ali Mortazavi,Sherman M. Weissman,John A. Stamatoyannopoulos,Michael Snyder,Roderic Guigó,Thomas R. Gingeras,David M. Gilbert,Ross C. Hardison,Michael A. Beer,Bing Ren +145 more
TL;DR: The mouse ENCODE Consortium has mapped transcription, DNase I hypersensitivity, transcription factor binding, chromatin modifications and replication domains throughout the mouse genome in diverse cell and tissue types as mentioned in this paper.
A comparative encyclopedia of DNA elements in the mouse genome - eScholarship
Miguel Ramalho-Santos,Yin Shen,Sheng Zhong,Licia Selleri,F Yue,Y Cheng,A Breschi,Jeff Vierstra,W Wu,T Ryba,Richard Sandstrom,Z Ma,C Davis,BD Pope +13 more
TL;DR: The laboratory mouse shares the majority of its protein-coding genes with humans, making it the premier model organism in biomedical research, yet the two mammals differ in significant ways.
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TL;DR: Functional data from multiple, diverse experiments performed on a targeted 1% of the human genome as part of the pilot phase of the ENCODE Project are reported, providing convincing evidence that the genome is pervasively transcribed, such that the majority of its bases can be found in primary transcripts.
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