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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：10/0  |  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  
Reshaping our understanding of species' roles in landscape-scale networks 期刊论文
ECOLOGY LETTERS, 2019, 22 (9) : 1367-1377
作者:  Hackett, Talya D.;  Sauve, Alix M. C.;  Davies, Nancy;  Montoya, Daniel;  Tylianakis, Jason M.;  Memmott, Jane
收藏  |  浏览/下载：10/0  |  提交时间：2019/11/27
Ecological networks  habitat diversity  herbivory  host-parasitoid interactions  landscape  multilayer networks  pollination  species roles  
Beyond the park and city dichotomy: Land use and land cover change in the northern coast of Sao Paulo (Brazil) 期刊论文
LANDSCAPE AND URBAN PLANNING, 2019, 189: 352-361
作者:  Pierri Daunt, Ana Beatriz;  Freire Silva, Thiago Sanna
收藏  |  浏览/下载：1/0  |  提交时间：2019/11/27
The OncoPPi network of cancer-focused protein-protein interactions to inform biological insights and therapeutic strategies 期刊论文
NATURE COMMUNICATIONS, 2017, 8
作者:  Li, Zenggang;  Ivanov, Andrei A.;  Su, Rina;  Gonzalez-Pecchi, Valentina;  Qi, Qi;  Liu, Songlin;  Webber, Philip;  McMillan, Elizabeth;  Rusnak, Lauren;  Pham, Cau;  Chen, Xiaoqian;  Mo, Xiulei;  Revennaugh, Brian;  Zhou, Wei;  Marcus, Adam;  Harati, Sahar;  Chen, Xiang;  Johns, Margaret A.;  White, Michael A.;  Moreno, Carlos;  Cooper, Lee A. D.;  Du, Yuhong;  Khuri, Fadlo R.;  Fu, Haian
收藏  |  浏览/下载：11/0  |  提交时间：2019/11/27
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：8/0  |  提交时间：2019/11/26
Meshed offshore grid  Supra-national TSO  Electricity market legislation  Network regulation  Offshore wind power  
Its all about connections: hubs and invasion in habitat networks 期刊论文
ECOLOGY LETTERS, 2019, 22 (2) : 313-321
作者:  Morel-Journel, Thibaut;  Assa, Claire Rais;  Mailleret, Ludovic;  Vercken, Elodie
收藏  |  浏览/下载：13/0  |  提交时间：2019/04/09
Allee effect  connectivity  establishment  hub  individual-based model  invasion  microcosm  network  simulation  spread  
Accelerating diffusion of climate-friendly technologies: A network perspective 期刊论文
ECOLOGICAL ECONOMICS, 2018, 152: 235-245
作者:  Halleck-Vega, Solmaria;  Mandel, Antoine;  Millock, Katrin
收藏  |  浏览/下载：6/0  |  提交时间：2019/04/09
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：0/0  |  提交时间：2019/11/27