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  • Cell Research
    Hefei Anhui 230027 China 2 Hefei National Laboratory for Physical Sciences at the Microscale Center for Integrative Imaging 443 Huang Shan Road Hefei Anhui 230027 China 3 Center for Biomedical Engineering University of Science and Technology of China 443 Huang Shan Road Hefei Anhui 230027 China Correspondence Gang Cai Tel Fax 86 551 63603802 E mail gcai ustc edu cn The Mediator complex plays an essential role in the regulation of eukaryotic transcription The Saccharomyces cerevisiae core Mediator comprises 21 subunits which are organized into Head Middle and Tail modules Previously the Head module was assigned to a distinct dense domain at the base and the Middle and Tail modules were identified to form a tight structure above the Head module which apparently contradicted findings from many biochemical and functional studies Here we compared the structures of the core Mediator and its subcomplexes especially the first 3D structure of the Head Middle modules which permitted an unambiguous assignment of the three modules Furthermore nanogold labeling pinpointing four Mediator subunits from different modules conclusively validated the modular assignment in which the Head and Middle modules fold back on one another and form the upper portion of the core Mediator while the

    Original URL path: http://www.cell-research.com/arts.asp?id=1951 (2016-02-14)
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  • Cell Research
    1 4 Lei Wang 1 Xiaoyong Fu 1 2 3 Agostina Nardone 1 2 3 Yongcheng Song 5 James Bradner 6 Nicholas Mitsiades 3 4 Constantine S Mitsiades 6 C Kent Osborne 1 2 3 Rachel Schiff 1 2 3 and Bert W O Malley 1 3 1 Department of Molecular and Cellular Biology Baylor College of Medicine Houston TX 77030 USA 2 Lester Sue Smith Breast Center Baylor College of Medicine Houston TX 77030 USA 3 Dan L Duncan Cancer Center Baylor College of Medicine Houston TX 77030 USA 4 Department of Medicine Hematology Oncology Baylor College of Medicine Houston TX 77030 USA 5 Department of Pharmacology Baylor College of Medicine Houston TX 77030 USA 6 Department of Medical Oncology Dana Farber Cancer Institute Department of Medicine Harvard Medical School Boston MA 02215 USA Correspondence Bert W O Malley E mail E mail berto bcm edu Tamoxifen has been a frontline treatment for estrogen receptor alpha ERα positive breast tumors in premenopausal women However resistance to tamoxifen occurs in many patients ER still plays a critical role in the growth of breast cancer cells with acquired tamoxifen resistance suggesting that ERα remains a valid target for treatment of tamoxifen resistant Tam R breast cancer In an effort to identify novel regulators of ERα signaling through a small scale siRNA screen against histone methyl modifiers we found WHSC1 a histone H3K36 methyltransferase as a positive regulator of ERα signaling in breast cancer cells We demonstrated that WHSC1 is recruited to the ERα gene by the BET protein BRD3 4 and facilitates ERα gene expression The small molecule BET protein inhibitor JQ1 potently suppressed the classic ERα signaling pathway and the growth of Tam R breast cancer cells in culture Using a Tam R breast cancer xenograft mouse model we demonstrated

    Original URL path: http://www.cell-research.com/arts.asp?id=1952 (2016-02-14)
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  • Cell Research
    Cambridge MA 02138 USA 2 Harvard Stem Cell Institute Harvard University 7 Divinity Avenue Cambridge MA 02138 USA 3 Center for Regenerative Medicine Massachusetts General Hospital 185 Cambridge Street Boston MA 021141 USA 4 Department of Medicine Cardiology Cell and Molecular Biology Karolinska Institutet SE 171 77 Stockholm Sweden 5 Department of Anesthesiology and Intensive Care Medicine Charité University Medicine Berlin Campus Charité Mitte Charitéplatz 1 10117 Berlin Germany Correspondence Makoto Sahara Tel 46 8 524 874 79 Fax 46 8 31 11 01 E mail makoto sahara ki se Kenneth R Chien Tel 46 8 524 874 67 Fax 46 8 31 11 01 E mail kenneth chien ki se Human pluripotent stem cell hPSC derived endothelial lineage cells constitutes a promising source for therapeutic revascularization but progress in this arena has been hampered by a lack of clinically scalable differentiation protocols and inefficient formation of a functional vessel network integrating with the host circulation upon transplantation Using a human embryonic stem cell reporter cell line where green fluorescent protein expression is driven by an endothelial cell specific VE cadherin VEC promoter we screened for 60 bioactive small molecules that would promote endothelial differentiation and found that administration of BMP4 and a GSK 3β inhibitor in an early phase and treatment with VEGF A and inhibition of the Notch signaling pathway in a later phase led to efficient differentiation of hPSCs to the endothelial lineage within six days This sequential approach generated 50 conversion of hPSCs to endothelial cells ECs specifically VEC CD31 CD34 CD14 KDRhigh endothelial progenitors EPs that exhibited higher angiogenic and clonogenic proliferation potential among endothelial lineage cells Pharmaceutical inhibition or genetical knockdown of Notch signaling in combination with VEGF A treatment resulted in efficient formation of EPs via KDR mesodermal precursors and blockade of the

    Original URL path: http://www.cell-research.com/arts.asp?id=1953 (2016-02-14)
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  • Cell Research
    a signature of translation FREE Yan Han 1 2 Xiangwei Gao 1 Botao Liu 3 Ji Wan 1 Xingqian Zhang 1 and Shu Bing Qian 1 1 Division of Nutritional Sciences Cornell University Ithaca NY 14853 USA 2 Department of Infectious Diseases Ruijin Hospital Shanghai Jiaotong University School of Medicine Shanghai 200025 China 3 Graduate Field of Genetics Genomics and Development Cornell University Ithaca NY 14853 USA Correspondence Shu Bing Qian E mail sq38 cornell edu The journey of a newly synthesized polypeptide starts in the peptidyltransferase center of the ribosome from where it traverses the exit tunnel The interior of the ribosome exit tunnel is neither straight nor smooth How the ribosome dynamics in vivo is influenced by the exit tunnel is poorly understood Genome wide ribosome profiling in mammalian cells reveals elevated ribosome density at the start codon and surprisingly the downstream 5th codon position as well We found that the highly focused ribosomal pausing shortly after initiation is attributed to the geometry of the exit tunnel as deletion of the loop region from ribosome protein L4 diminishes translational pausing at the 5th codon position Unexpectedly the ribosome variant undergoes translational abandonment shortly after initiation suggesting that there

    Original URL path: http://www.cell-research.com/arts.asp?id=1954 (2016-02-14)
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  • Cell Research
    Beijing 100049 China 3 State Key Laboratory of Molecular Developmental Biology Institute of Genetics and Developmental Biology Chinese Academy of Sciences Beijing 100101 China 4 College of Life Sciences Hebei United University Tangshan Hebei 063000 China Correspondence Wei Li Tel 86 10 64807529 Fax 86 10 64806480 E mail leways ioz ac cn Fei Gao Tel 86 10 64807593 Fax 86 10 64806480 E mail gaof ioz ac cn The acrosome is a specialized organelle that covers the anterior part of the sperm nucleus and plays an essential role in the process of fertilization The molecular mechanism underlying the biogenesis of this lysosome related organelle LRO is still largely unknown Here we show that germ cell specific Atg7 knockout mice were infertile due to a defect in acrosome biogenesis and displayed a phenotype similar to human globozoospermia this reproductive defect was successfully rescued by intracytoplasmic sperm injections Furthermore the depletion of Atg7 in germ cells did not affect the early stages of development of germ cells but at later stages of spermatogenesis the proacrosomal vesicles failed to fuse into a single acrosomal vesicle during the Golgi phase which finally resulted in irregular or nearly round headed spermatozoa Autophagic flux was

    Original URL path: http://www.cell-research.com/arts.asp?id=1955 (2016-02-14)
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  • Cell Research
    Case Comprehensive Cancer Center Case Western Reserve University Cleveland OH 44106 USA Correspondence Bibo Li Tel 1 216 687 2444 E mail b li37 csuohio edu Subtelomeres consist of sequences adjacent to telomeres and contain genes involved in important cellular functions as subtelomere instability is associated with several human diseases Balancing between subtelomere stability and plasticity is particularly important for Trypanosoma brucei a protozoan parasite that causes human African trypanosomiasis T brucei regularly switches its major variant surface antigen variant surface glycoprotein VSG to evade the host immune response and VSGs are expressed exclusively from subtelomeres in a strictly monoallelic fashion Telomere proteins are important for protecting chromosome ends from illegitimate DNA processes However whether they contribute to subtelomere integrity and stability has not been well studied We have identified a novel T brucei telomere protein T brucei TRF Interacting Factor 2 TbTIF2 as a functional homolog of mammalian TIN2 A transient depletion of TbTIF2 led to an elevated VSG switching frequency and an increased amount of DNA double strand breaks DSBs in both active and silent subtelomeric bloodstream form expression sites BESs Therefore TbTIF2 plays an important role in VSG switching regulation and is important for subtelomere integrity and

    Original URL path: http://www.cell-research.com/arts.asp?id=1956 (2016-02-14)
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  • Cell Research
    School of Life Sciences Peking University Beijing China 2 Institute of Molecular Medicine Peking University Beijing China Correspondence Dong Liu E mail E mail doliu pku edu cn Type II clustered regularly interspaced short palindromic repeat CRISPR associated Cas system is a novel genome editing tool for targeted mutagenesis in cultured cells and whole organisms1 2 3 Recently the CRISPR Cas9 system has been applied in C elegans using various

    Original URL path: http://www.cell-research.com/arts.asp?id=1957 (2016-02-14)
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  • Cell Research
    Gong 1 Jihui Wu 1 and Yunyu Shi 1 1 Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences University of Science and Technology of China Hefei Anhui 230026 China 2 Biomedical Research Institute Shenzhen PKU HKUST Medical Center Shenzhen Guangdong 518036 China Correspondence Jihui Wu E mail wujihui ustc edu cn Yunyu Shi E mail E mail yyshi ustc edu cn The eukaryotic genome is

    Original URL path: http://www.cell-research.com/arts.asp?id=1958 (2016-02-14)
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