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HBO1 is required for the maintenance of leukaemia stem cells 期刊论文
NATURE, 2020, 577 (7789) : 266-+
作者:  MacPherson, Laura;  Anokye, Juliana;  Yeung, Miriam M.;  Lam, Enid Y. N.;  Chan, Yih-Chih;  Weng, Chen-Fang;  Yeh, Paul;  Knezevic, Kathy;  Butler, Miriam S.;  Hoegl, Annabelle;  Chan, Kah-Lok;  Burr, Marian L.;  Gearing, Linden J.;  Willson, Tracy;  Liu, Joy;  Choi, Jarny;  Yang, Yuqing;  Bilardi, Rebecca A.;  Falk, Hendrik;  Nghi Nguyen;  Stupple, Paul A.;  Peat, Thomas S.;  Zhang, Ming;  de Silva, Melanie;  Carrasco-Pozo, Catalina;  Avery, Vicky M.;  Khoo, Poh Sim;  Dolezal, Olan;  Dennis, Matthew L.;  Nuttall, Stewart;  Surjadi, Regina;  Newman, Janet;  Ren, Bin;  Leaver, David J.;  Sun, Yuxin;  Baell, Jonathan B.;  Dovey, Oliver;  Vassiliou, George S.;  Grebien, Florian;  Dawson, Sarah-Jane;  Street, Ian P.;  Monahan, Brendon J.;  Burns, Christopher J.;  Choudhary, Chunaram;  Blewitt, Marnie E.;  Voss, Anne K.;  Thomas, Tim;  Dawson, Mark A.
收藏  |  浏览/下载:58/0  |  提交时间:2020/07/03

Acute myeloid leukaemia (AML) is a heterogeneous disease characterized by transcriptional dysregulation that results in a block in differentiation and increased malignant self-renewal. Various epigenetic therapies aimed at reversing these hallmarks of AML have progressed into clinical trials, but most show only modest efficacy owing to an inability to effectively eradicate leukaemia stem cells (LSCs)(1). Here, to specifically identify novel dependencies in LSCs, we screened a bespoke library of small hairpin RNAs that target chromatin regulators in a unique ex vivo mouse model of LSCs. We identify the MYST acetyltransferase HBO1 (also known as KAT7 or MYST2) and several known members of the HBO1 protein complex as critical regulators of LSC maintenance. Using CRISPR domain screening and quantitative mass spectrometry, we identified the histone acetyltransferase domain of HBO1 as being essential in the acetylation of histone H3 at K14. H3 acetylated at K14 (H3K14ac) facilitates the processivity of RNA polymerase II to maintain the high expression of key genes (including Hoxa9 and Hoxa10) that help to sustain the functional properties of LSCs. To leverage this dependency therapeutically, we developed a highly potent small-molecule inhibitor of HBO1 and demonstrate its mode of activity as a competitive analogue of acetyl-CoA. Inhibition of HBO1 phenocopied our genetic data and showed efficacy in a broad range of human cell lines and primary AML cells from patients. These biological, structural and chemical insights into a therapeutic target in AML will enable the clinical translation of these findings.


  
Mass-spectrometry-based draft of the Arabidopsis proteome 期刊论文
NATURE, 2020
作者:  Vasanthakumar, Ajithkumar;  Chisanga, David;  Blume, Jonas;  Gloury, Renee;  Britt, Kara;  Henstridge, Darren C.;  Zhan, Yifan;  Torres, Santiago Valle;  Liene, Sebastian;  Collins, Nicholas;  Cao, Enyuan;  Sidwell, Tom;  Li, Chaoran;  Spallanzani, Raul German;  Liao, Yang;  Beavis, Paul A.;  Gebhardt, Thomas;  Trevaskis, Natalie;  Nutt, Stephen L.;  Zajac, Jeffrey D.;  Davey, Rachel A.;  Febbraio, Mark A.;  Mathis, Diane;  Shi, Wei;  Kallies, Axel
收藏  |  浏览/下载:62/0  |  提交时间:2020/07/03

Plants are essential for life and are extremely diverse organisms with unique molecular capabilities(1). Here we present a quantitative atlas of the transcriptomes, proteomes and phosphoproteomes of 30 tissues of the model plant Arabidopsis thaliana. Our analysis provides initial answers to how many genes exist as proteins (more than 18,000), where they are expressed, in which approximate quantities (a dynamic range of more than six orders of magnitude) and to what extent they are phosphorylated (over 43,000 sites). We present examples of how the data may be used, such as to discover proteins that are translated from short open-reading frames, to uncover sequence motifs that are involved in the regulation of protein production, and to identify tissue-specific protein complexes or phosphorylation-mediated signalling events. Interactive access to this resource for the plant community is provided by the ProteomicsDB and ATHENA databases, which include powerful bioinformatics tools to explore and characterize Arabidopsis proteins, their modifications and interactions.


A quantitative atlas of the transcriptomes, proteomes and phosphoproteomes of 30 tissues of the model plant Arabidopsis thaliana provides a valuable resource for plant research.


  
A mother's legacy: the strength of maternal effects in animal populations 期刊论文
ECOLOGY LETTERS, 2019, 22 (10) : 1620-1628
作者:  Moore, Michael P.;  Whiteman, Howard H.;  Martin, Ryan A.
收藏  |  浏览/下载:17/0  |  提交时间:2019/11/27
Animal model  life-history theory  meta-analysis  quantitative genetics  
The dual-credit policy: Quantifying the policy impact on plug-in electric vehicle sales and industry profits in China 期刊论文
ENERGY POLICY, 2018, 121: 597-610
作者:  Ou, Shiqi;  Lin, Zhenhong;  Qi, Liang;  Li, Jie;  He, Xin;  Przesmitzki, Steven
收藏  |  浏览/下载:19/0  |  提交时间:2019/04/09
China'  s vehicle market  Policy analysis  Quantitative model  Corporate average fuel consumption  Plug-in electric vehicle  Industry profits  
How to find a reasonable energy transition strategy in Korea?: Quantitative analysis based on power market simulation 期刊论文
ENERGY POLICY, 2018, 119: 396-409
作者:  Song, Yong Hyun;  Kim, Hyun Joong;  Kim, Seung Wan;  Jin, Young Gyu;  Yoon, Yong Tae
收藏  |  浏览/下载:13/0  |  提交时间:2019/04/09
Korea  Energy transition  Quantitative analysis  Market operation model  Cost-based pool