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Impaired cell fate through gain-of-function mutations in a chromatin reader 期刊论文
NATURE, 2020, 577 (7788) : 121-+
作者:  Wan, Liling;  Chong, Shasha;  Xuan, Fan;  Liang, Angela;  Cui, Xiaodong;  Gates, Leah;  Carroll, Thomas S.;  Li, Yuanyuan;  Feng, Lijuan;  Chen, Guochao;  Wang, Shu-Ping;  Ortiz, Michael V.;  Daley, Sara K.;  Wang, Xiaolu;  Xuan, Hongwen;  Kentsis, Alex;  Muir, Tom W.;  Roeder, Robert G.;  Li, Haitao;  Li, Wei;  Tjian, Robert;  Wen, Hong;  Allis, C. David
收藏  |  浏览/下载：11/0  |  提交时间：2020/07/03

Modifications of histone proteins have essential roles in normal development and human disease. Recognition of modified histones by '  reader'  proteins is a key mechanism that mediates the function of histone modifications, but how the dysregulation of these readers might contribute to disease remains poorly understood. We previously identified the ENL protein as a reader of histone acetylation via its YEATS domain, linking it to the expression of cancer-driving genes in acute leukaemia1. Recurrent hotspot mutations have been found in the ENL YEATS domain in Wilms tumour2,3, the most common type of paediatric kidney cancer. Here we show, using human and mouse cells, that these mutations impair cell-fate regulation by conferring gain-of-function in chromatin recruitment and transcriptional control. ENL mutants induce gene-expression changes that favour a premalignant cell fate, and, in an assay for nephrogenesis using murine cells, result in undifferentiated structures resembling those observed in human Wilms tumour. Mechanistically, although bound to largely similar genomic loci as the wild-type protein, ENL mutants exhibit increased occupancy at a subset of targets, leading to a marked increase in the recruitment and activity of transcription elongation machinery that enforces active transcription from target loci. Furthermore, ectopically expressed ENL mutants exhibit greater self-association and form discrete and dynamic nuclear puncta that are characteristic of biomolecular hubs consisting of local high concentrations of regulatory factors. Such mutation-driven ENL self-association is functionally linked to enhanced chromatin occupancy and gene activation. Collectively, our findings show that hotspot mutations in a chromatinreader domain drive self-reinforced recruitment, derailing normal cell-fate control during development and leading to an oncogenic outcome.


  
Wastewater management strategies for sustained shale gas production 期刊论文
ENVIRONMENTAL RESEARCH LETTERS, 2020, 15 (2)
作者:  Menefee, Anne H.;  Ellis, Brian R.
收藏  |  浏览/下载：7/0  |  提交时间：2020/07/02
shale gas  hydraulic fracturing  wastewater management  
yyy HUMAN GENOMICS Chromatin three-dimensional interactions mediate genetic effects on gene expression 期刊论文
SCIENCE, 2019, 364 (6439) : 452-+
作者:  Delaneau, O.;  Zazhytska, M.;  Borel, C.;  Giannuzzi, G.;  Rey, G.;  Howald, C.;  Kumar, S.;  Ongen, H.;  Popadin, K.;  Marbach, D.;  Ambrosini, G.;  Bielser, D.;  Hacker, D.;  Romano, L.;  Ribaux, P.;  Wiederkehr, M.;  Falconnet, E.;  Bucher, P.;  Bergmann, S.;  Antonarakis, S. E.;  Reymond, A.;  Dermitzakis, E. T.
收藏  |  浏览/下载：4/0  |  提交时间：2019/11/27
A supra-national TSO to enhance offshore wind power development in the Baltic Sea? A legal and regulatory analysis 期刊论文
ENERGY POLICY, 2019, 128: 775-782
作者:  Sunila, Kanerva;  Bergaentzle, Claire;  Martin, Benedicte;  Ekroos, Ari
收藏  |  浏览/下载：9/0  |  提交时间：2019/11/26
Meshed offshore grid  Supra-national TSO  Electricity market legislation  Network regulation  Offshore wind power  
Developmental enhancers and chromosome topology 期刊论文
SCIENCE, 2018, 361 (6409) : 1341-1345
作者:  Furlong, Eileen E. M.;  Levine, Michael
收藏  |  浏览/下载：1/0  |  提交时间：2019/11/27
Imaging dynamic and selective low-complexity domain interactions that control gene transcription 期刊论文
SCIENCE, 2018, 361 (6400)
作者:  Chong, Shasha;  Dugast-Darzacq, Claire;  Liu, Zhe;  Dong, Peng;  Dailey, Gina M.;  Cattoglio, Claudia;  Heckert, Alec;  Banala, Sambashiva;  Lavis, Luke;  Darzacq, Xavier;  Tjian, Robert
收藏  |  浏览/下载：8/0  |  提交时间：2019/11/27
County-level climate change information to support decision-making on working lands 期刊论文
CLIMATIC CHANGE, 2018, 148 (3) : 355-369
作者:  Elias, Emile;  Schrader, T. Scott;  Abatzoglou, John T.;  James, Darren;  Crimmins, Mike;  Weiss, Jeremy;  Rango, Albert
收藏  |  浏览/下载：5/0  |  提交时间：2019/04/09
Climate change  Decision-making  Agriculture  Forestry  Ranching  USDA climate hubs  Cooperative extension  
SLAM-seq defines direct gene-regulatory functions of the BRD4-MYC axis 期刊论文
SCIENCE, 2018, 360 (6390) : 800-805
作者:  Muhar, Matthias;  Ebert, Anja;  Neumann, Tobias;  Umkehrer, Christian;  Jude, Julian;  Wieshofer, Corinna;  Rescheneder, Philipp;  Lipp, Jesse J.;  Herzog, Veronika A.;  Reichholf, Brian;  Cisneros, David A.;  Hoffmann, Thomas;  Schlapansky, Moritz F.;  Bhat, Pooja;  von Haeseler, Arndt;  Koecher, Thomas;  Obenauf, Anna C.;  Popow, Johannes;  Ameres, Stefan L.;  Zuber, Johannes
收藏  |  浏览/下载：13/0  |  提交时间：2019/11/27
Systematic analysis of complex genetic interactions 期刊论文
SCIENCE, 2018, 360 (6386)
作者:  Kuzmin, Elena;  VanderSluis, Benjamin;  Wang, Wen;  Tan, Guihong;  Deshpande, Raamesh;  Chen, Yiqun;  Usaj, Matej;  Balint, Attila;  Usaj, Mojca Mattiazzi;  van Leeuwen, Jolanda;  Koch, Elizabeth N.;  Pons, Carles;  Dagilis, Andrius J.;  Pryszlak, Michael;  YangWang, Jason Zi;  Hanchard, Julia;  Riggi, Margot;  Xu, Kaicong;  Heydari, Hamed;  Luis, Bryan-Joseph San;  Shuteriqi, Ermira;  Zhu, Hongwei;  Van Dyk, Nydia;  Sharifpoor, Sara;  Costanzo, Michael;  Loewith, Robbie;  Caudy, Amy;  Bolnick, Daniel;  Brown, Grant W.;  Andrews, Brenda J.;  Boone, Charles;  Myers, Chad L.
收藏  |  浏览/下载：12/0  |  提交时间：2019/11/27
A 'Regional Energy Hub' for achieving a low-carbon energy transition 期刊论文
ENERGY POLICY, 2018, 113: 376-385
作者:  Guler, Burak;  Celebi, Emre;  Nathwani, Jatin
收藏  |  浏览/下载：5/0  |  提交时间：2019/04/09
Electricity markets  Transmission investment  Regional energy hub  Low-carbon energy economy