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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.


  
Examining forest resilience to changing fire frequency in a fire-prone region of boreal forest 期刊论文
GLOBAL CHANGE BIOLOGY, 2019, 25 (3) : 869-884
作者:  Hart, Sarah J.;  Henkelnnan, Jonathan;  McLoughlin, Philip D.;  Nielsen, Scott E.;  Truchon-Savard, Alexandre;  Johnstone, Jill F.
收藏  |  浏览/下载：6/0  |  提交时间：2019/04/09
alternative stable state  black spruce  climate change  immaturity risk  jack pine  resistance  self-regulation  spatially explicit state-and-transition simulation model  
Single-cell profiling identifies myeloid cell subsets with distinct fates during neuroinflammation 期刊论文
SCIENCE, 2019, 363 (6425) : 365-+
作者:  Costa Jordao, Marta Joana;  Sankowski, Roman;  Brendecke, Stefanie M.;  Sagar;  Locatelli, Giuseppe;  Tai, Yi-Heng;  Tay, Tuan Leng;  Schramm, Eva;  Armbruster, Stephan;  Hagemeyer, Nora;  Gross, Olaf;  Mai, Dominic;  Cicek, Ozgun;  Falk, Thorsten;  Kerschensteiner, Martin;  Grun, Dominic;  Prinz, Marco
收藏  |  浏览/下载：14/0  |  提交时间：2019/11/27
FTSJ3 is an RNA 2 '-O-methyltransferase recruited by HIV to avoid innate immune sensing 期刊论文
NATURE, 2019, 565 (7740) : 500-+
作者:  Ringeard, Mathieu;  Marchand, Virginie;  Decroly, Etienne;  Motorin, Yuri;  Bennasser, Yamina
收藏  |  浏览/下载：1/0  |  提交时间：2019/11/27
Lipid-mediated PX-BAR domain recruitment couples local membrane constriction to endocytic vesicle fission 期刊论文
NATURE COMMUNICATIONS, 2017, 8
作者:  Schoeneberg, Johannes;  Lehmann, Martin;  Ullrich, Alexander;  Posor, York;  Lo, Wen-Ting;  Lichtner, Gregor;  Schmoranzer, Jan;  Haucke, Volker;  Noe, Frank
收藏  |  浏览/下载：9/0  |  提交时间：2019/11/27
Demographic costs and benefits of natural regeneration during tropical forest restoration 期刊论文
ECOLOGY LETTERS, 2019, 22 (1) : 34-44
作者:  Caughlin, T. Trevor;  de la Pena-Domene, Marines;  Martinez-Garza, Cristina
收藏  |  浏览/下载：4/0  |  提交时间：2019/04/09
Demographic model  early succession  full life-cycle analysis  individual-based model  life-history categories  natural regeneration  population-level  reforestation  successional age  tropical forest restoration  
Relative size to resprouters determines post-fire recruitment of non-serotinous pines 期刊论文
FOREST ECOLOGY AND MANAGEMENT, 2018, 429: 300-307
作者:  Sanchez-Pinillos, Martina;  Ameztegui, Aitor;  Kitzberger, Thomas;  Coll, Lluis
收藏  |  浏览/下载：13/0  |  提交时间：2019/04/09
Plant-plant interactions  Competition  Water limitation  Mixed Mediterranean forest  Pinta nigra  Quercus  
Germinal center antibody mutation trajectories are determined by rapid self/foreign discrimination 期刊论文
SCIENCE, 2018, 360 (6385) : 223-226
作者:  Burnett, Deborah L.;  Langley, David B.;  Schofield, Peter;  Hermes, Jana R.;  Chan, Tyani D.;  Jackson, Jennifer;  Bourne, Katherine;  Reed, Joanne H.;  Patterson, Kate;  Porebski, Benjamin T.;  Brink, Robert;  Christ, Daniel;  Goodnow, Christopher C.
收藏  |  浏览/下载：7/0  |  提交时间：2019/11/27
Node self-connections and metapopulation persistence: reply to Saura (2018) 期刊论文
ECOLOGY LETTERS, 2018, 21 (4) : 605-606
作者:  Zamborain-Mason, Jessica;  Russ, Garry R.;  Abesamis, Rene A.;  Bucol, Abner A.;  Connolly, Sean R.
收藏  |  浏览/下载：4/0  |  提交时间：2019/04/09
Conservation planning  habitat area  habitat availability  habitat quality  local retention  metapopulation viability  network metrics  network theory  reserve networks  self-recruitment  
Network theory and metapopulation persistence: incorporating node self-connections 期刊论文
ECOLOGY LETTERS, 2017, 20 (7)
作者:  Zamborain-Mason, Jessica;  Russ, Garry R.;  Abesamis, Rene A.;  Bucol, Abner A.;  Connolly, Sean R.
收藏  |  浏览/下载：6/0  |  提交时间：2019/04/09
Conservation planning  local retention  metapopulation persistence  network metrics  network theory  reserve networks  self-recruitment