Translocations affecting the chromosomal locus 11q23 are hallmarks of infant leukemias. These events disrupt the MLL gene (also ALL-1 or HRX) and fuse the MLL amino terminus in frame with a variety of unrelated proteins. The ENL gene on 19p13.1 is a recurrent fusion partner of MLL. Whereas potential functions have been suggested for isolated domains of either MLL or ENL no experimental data exist for the biological properties of the complete chimeric MLL-ENL protein. We show here that the fusion of MLL with ENL creates a novel molecule that is a potent general transcriptional transactivator in transient reporter gene assays. MLL-ENL strongly transactivated several unrelated promoters including the promoter of Hoxa7 a potential target gene for the unaltered MLL protein. This transactivation capability was cell type specific and it was critically dependent on the contributions of the methyltransferase-homology (MT) region of MLL in combination with the C-terminus of ENL. Squelching experiments and gel retardation studies identified the ENL C-terminus as a binding partner for an unknown factor and the MLL MT region as a unique general DNA binding motif. The potential implications of these findings for the leukemogenesis by MLL-ENL are discussed.
机构:
Rui Jin Hosp, Shanghai Inst Hematol, State Lab Med Genom, Shanghai, Peoples R ChinaRui Jin Hosp, Shanghai Inst Hematol, State Lab Med Genom, Shanghai, Peoples R China
Liu, H
Chen, B
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Rui Jin Hosp, Shanghai Inst Hematol, State Lab Med Genom, Shanghai, Peoples R ChinaRui Jin Hosp, Shanghai Inst Hematol, State Lab Med Genom, Shanghai, Peoples R China
Chen, B
Xiong, H
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Rui Jin Hosp, Shanghai Inst Hematol, State Lab Med Genom, Shanghai, Peoples R ChinaRui Jin Hosp, Shanghai Inst Hematol, State Lab Med Genom, Shanghai, Peoples R China
Xiong, H
Huang, QH
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Rui Jin Hosp, Shanghai Inst Hematol, State Lab Med Genom, Shanghai, Peoples R ChinaRui Jin Hosp, Shanghai Inst Hematol, State Lab Med Genom, Shanghai, Peoples R China
Huang, QH
Zhang, QH
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Rui Jin Hosp, Shanghai Inst Hematol, State Lab Med Genom, Shanghai, Peoples R ChinaRui Jin Hosp, Shanghai Inst Hematol, State Lab Med Genom, Shanghai, Peoples R China
Zhang, QH
Wang, ZG
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Rui Jin Hosp, Shanghai Inst Hematol, State Lab Med Genom, Shanghai, Peoples R ChinaRui Jin Hosp, Shanghai Inst Hematol, State Lab Med Genom, Shanghai, Peoples R China
Wang, ZG
Chen, Z
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Rui Jin Hosp, Shanghai Inst Hematol, State Lab Med Genom, Shanghai, Peoples R ChinaRui Jin Hosp, Shanghai Inst Hematol, State Lab Med Genom, Shanghai, Peoples R China
Chen, Z
Chen, SJ
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Rui Jin Hosp, Shanghai Inst Hematol, State Lab Med Genom, Shanghai, Peoples R ChinaRui Jin Hosp, Shanghai Inst Hematol, State Lab Med Genom, Shanghai, Peoples R China
机构:
Univ Penn, Sch Vet Med, Dept Biomed Sci, Philadelphia, PA 19104 USA
Univ Penn, Perelman Sch Med, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USAUniv Penn, Sch Vet Med, Dept Biomed Sci, Philadelphia, PA 19104 USA
Yan, Fangxue
Li, Jinyang
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Univ Penn, Perelman Sch Med, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USAUniv Penn, Sch Vet Med, Dept Biomed Sci, Philadelphia, PA 19104 USA
Li, Jinyang
Milosevic, Jelena
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Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USAUniv Penn, Sch Vet Med, Dept Biomed Sci, Philadelphia, PA 19104 USA
Milosevic, Jelena
Petroni, Ricardo
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Univ Penn, Sch Vet Med, Dept Biomed Sci, Philadelphia, PA 19104 USAUniv Penn, Sch Vet Med, Dept Biomed Sci, Philadelphia, PA 19104 USA
Petroni, Ricardo
Liu, Suying
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Univ Penn, Perelman Sch Med, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA
Univ Penn, Perelman Sch Med, Dept Canc Biol, Philadelphia, PA 19104 USAUniv Penn, Sch Vet Med, Dept Biomed Sci, Philadelphia, PA 19104 USA
Liu, Suying
Shi, Zhennan
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Fudan Univ, Shanghai Key Lab Med Epigenet, Inst Biomed Sci, Int Colab Med Epigenet & Metab,Minist Sci & Techn, Shanghai, Peoples R China
Fudan Univ, Liver Canc Inst, Minist Educ, Key Lab Carcinogenesis & Canc Invas,Zhongshan Hos, Shanghai, Peoples R ChinaUniv Penn, Sch Vet Med, Dept Biomed Sci, Philadelphia, PA 19104 USA
Shi, Zhennan
Yuan, Salina
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Univ Penn, Perelman Sch Med, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USAUniv Penn, Sch Vet Med, Dept Biomed Sci, Philadelphia, PA 19104 USA
Yuan, Salina
Reynaga, Janice M.
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Univ Penn, Sch Vet Med, Dept Biomed Sci, Philadelphia, PA 19104 USAUniv Penn, Sch Vet Med, Dept Biomed Sci, Philadelphia, PA 19104 USA
Reynaga, Janice M.
Qi, Yuwei
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Univ Penn, Perelman Sch Med, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USAUniv Penn, Sch Vet Med, Dept Biomed Sci, Philadelphia, PA 19104 USA
Qi, Yuwei
Rico, Joshua
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Univ Penn, Sch Vet Med, Dept Biomed Sci, Philadelphia, PA 19104 USAUniv Penn, Sch Vet Med, Dept Biomed Sci, Philadelphia, PA 19104 USA
Rico, Joshua
Yu, Sixiang
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机构:
Univ Penn, Perelman Sch Med, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA
Univ Penn, Perelman Sch Med, Dept Canc Biol, Philadelphia, PA 19104 USAUniv Penn, Sch Vet Med, Dept Biomed Sci, Philadelphia, PA 19104 USA
Yu, Sixiang
Liu, Yiman
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机构:
Univ Penn, Perelman Sch Med, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA
Univ Penn, Perelman Sch Med, Dept Canc Biol, Philadelphia, PA 19104 USA
Univ Penn, Perelman Sch Med, Penn Epigenet Inst, Philadelphia, PA 19104 USAUniv Penn, Sch Vet Med, Dept Biomed Sci, Philadelphia, PA 19104 USA
Liu, Yiman
Rokudai, Susumu
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机构:
Gunma Univ, Dept Mol Pharmacol & Oncol, Gunma, JapanUniv Penn, Sch Vet Med, Dept Biomed Sci, Philadelphia, PA 19104 USA
Rokudai, Susumu
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机构:
Palmisiano, Neil
Meyer, Sara E.
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机构:
Thomas Jefferson Univ, Sidney Kimmel Canc Ctr, Dept Canc Biol, Philadelphia, PA 19107 USAUniv Penn, Sch Vet Med, Dept Biomed Sci, Philadelphia, PA 19104 USA
Meyer, Sara E.
Sung, Pamela J.
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机构:
Univ Penn, Div Hematol Oncol, Philadelphia, PA 19104 USA
Roswell Park Comprehens Canc Ctr, Dept Med, Buffalo, NY USAUniv Penn, Sch Vet Med, Dept Biomed Sci, Philadelphia, PA 19104 USA
Sung, Pamela J.
Wan, Liling
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机构:
Univ Penn, Perelman Sch Med, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA
Univ Penn, Perelman Sch Med, Dept Canc Biol, Philadelphia, PA 19104 USA
Univ Penn, Perelman Sch Med, Penn Epigenet Inst, Philadelphia, PA 19104 USAUniv Penn, Sch Vet Med, Dept Biomed Sci, Philadelphia, PA 19104 USA
Wan, Liling
Lan, Fei
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机构:
Fudan Univ, Shanghai Key Lab Med Epigenet, Inst Biomed Sci, Int Colab Med Epigenet & Metab,Minist Sci & Techn, Shanghai, Peoples R China
Fudan Univ, Liver Canc Inst, Minist Educ, Key Lab Carcinogenesis & Canc Invas,Zhongshan Hos, Shanghai, Peoples R ChinaUniv Penn, Sch Vet Med, Dept Biomed Sci, Philadelphia, PA 19104 USA
Lan, Fei
Garcia, Benjamin A.
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机构:
Univ Penn, Perelman Sch Med, Penn Epigenet Inst, Philadelphia, PA 19104 USAUniv Penn, Sch Vet Med, Dept Biomed Sci, Philadelphia, PA 19104 USA
Garcia, Benjamin A.
Stanger, Ben Z.
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机构:
Univ Penn, Perelman Sch Med, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA
Univ Penn, Perelman Sch Med, Dept Med, Philadelphia, PA 19104 USAUniv Penn, Sch Vet Med, Dept Biomed Sci, Philadelphia, PA 19104 USA
Stanger, Ben Z.
Sykes, David B.
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机构:
Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA
Havard Stem Cell Inst, Cambridge, MA 02138 USAUniv Penn, Sch Vet Med, Dept Biomed Sci, Philadelphia, PA 19104 USA
Sykes, David B.
Blanco, M. Andres
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机构:
Univ Penn, Sch Vet Med, Dept Biomed Sci, Philadelphia, PA 19104 USAUniv Penn, Sch Vet Med, Dept Biomed Sci, Philadelphia, PA 19104 USA