Genome-wide nucleosome specificity and function of chromatin remodellers in ES cells
Maud de Dieuleveult,Kuangyu Yen,Kuangyu Yen,Isabelle Hmitou,Arnaud Depaux,Fayçal Boussouar,Daria Bou Dargham,Sylvie Jounier,Hélène Humbertclaude,Florence Ribierre,Céline Baulard,Nina Farrell,Bongsoo Park,Céline Keime,Lucie Carrière,Soizick Berlivet,Marta Gut,Ivo Gut,Michel Werner,Jean-François Deleuze,Robert Olaso,Jean-Christophe Aude,Sophie Chantalat,B. Franklin Pugh,Matthieu Gérard +24 more
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TLDR
Findings indicate that remodellers target specific nucleosomes at the edge of NFRs, where they regulate ES cell transcriptional programs.Abstract:
ATP-dependent chromatin remodellers allow access to DNA for transcription factors and the general transcription machinery, but whether mammalian chromatin remodellers target specific nucleosomes to regulate transcription is unclear. Here we present genome-wide remodeller-nucleosome interaction profiles for the chromatin remodellers Chd1, Chd2, Chd4, Chd6, Chd8, Chd9, Brg1 and Ep400 in mouse embryonic stem (ES) cells. These remodellers bind one or both full nucleosomes that flank micrococcal nuclease (MNase)-defined nucleosome-free promoter regions (NFRs), where they separate divergent transcription. Surprisingly, large CpG-rich NFRs that extend downstream of annotated transcriptional start sites are nevertheless bound by non-nucleosomal or subnucleosomal histone variants (H3.3 and H2A.Z) and marked by H3K4me3 and H3K27ac modifications. RNA polymerase II therefore navigates hundreds of base pairs of altered chromatin in the sense direction before encountering an MNase-resistant nucleosome at the 3' end of the NFR. Transcriptome analysis after remodeller depletion reveals reciprocal mechanisms of transcriptional regulation by remodellers. Whereas at active genes individual remodellers have either positive or negative roles via altering nucleosome stability, at polycomb-enriched bivalent genes the same remodellers act in an opposite manner. These findings indicate that remodellers target specific nucleosomes at the edge of NFRs, where they regulate ES cell transcriptional programs.read more
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Gene discovery and polygenic prediction from a genome-wide association study of educational attainment in 1.1 million individuals
James J. Lee,Robbee Wedow,Aysu Okbay,Edward Kong,Omeed Maghzian,Meghan Zacher,Tuan Anh Nguyen-Viet,Peter Bowers,Julia Sidorenko,Julia Sidorenko,Richard Karlsson Linnér,Richard Karlsson Linnér,Mark Alan Fontana,Mark Alan Fontana,Tushar Kundu,Chanwook Lee,Hui Li,Ruoxi Li,Rebecca Royer,Pascal Timshel,Pascal Timshel,Raymond K. Walters,Raymond K. Walters,Emily A. Willoughby,Loic Yengo,Maris Alver,Yanchun Bao,David W. Clark,Felix R. Day,Nicholas A. Furlotte,Peter K. Joshi,Peter K. Joshi,Kathryn E. Kemper,Aaron Kleinman,Claudia Langenberg,Reedik Mägi,Joey W. Trampush,Shefali S. Verma,Yang Wu,Max Lam,Jing Hua Zhao,Zhili Zheng,Zhili Zheng,Jason D. Boardman,Harry Campbell,Jeremy Freese,Kathleen Mullan Harris,Caroline Hayward,Pamela Herd,Pamela Herd,Meena Kumari,Todd Lencz,Todd Lencz,Jian'an Luan,Anil K. Malhotra,Anil K. Malhotra,Andres Metspalu,Lili Milani,Ken K. Ong,John R. B. Perry,David J. Porteous,Marylyn D. Ritchie,Melissa C. Smart,Blair H. Smith,Joyce Y. Tung,Nicholas J. Wareham,James F. Wilson,Jonathan P. Beauchamp,Dalton Conley,Tõnu Esko,Steven F. Lehrer,Steven F. Lehrer,Steven F. Lehrer,Patrik K. E. Magnusson,Sven Oskarsson,Tune H. Pers,Tune H. Pers,Matthew R. Robinson,Matthew R. Robinson,Kevin Thom,Chelsea Watson,Christopher F. Chabris,Michelle N. Meyer,David Laibson,Jian Yang,Magnus Johannesson,Philipp Koellinger,Philipp Koellinger,Patrick Turley,Patrick Turley,Peter M. Visscher,Daniel J. Benjamin,Daniel J. Benjamin,David Cesarini,David Cesarini +94 more
TL;DR: A joint (multi-phenotype) analysis of educational attainment and three related cognitive phenotypes generates polygenic scores that explain 11–13% of the variance ineducational attainment and 7–10% ofthe variance in cognitive performance, which substantially increases the utility ofpolygenic scores as tools in research.
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Understanding nucleosome dynamics and their links to gene expression and DNA replication.
TL;DR: Nucleosome dynamics are governed by a complex interplay of histone composition, histone post-translational modifications, nucleosome occupancy and positioning within chromatin, which are influenced by numerous regulatory factors, including general Regulatory factors, chromatin remodellers, chaperones and polymerases.
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Ping Wang,Ryan Mokhtari,Erika Pedrosa,Michael Kirschenbaum,Can Bayrak,Deyou Zheng,Herbert M. Lachman +6 more
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