Role of UTX in retinoic acid receptor-mediated gene regulation in leukemia
Human UTX, a member of the Jumonji C family of proteins, associates with mixed-lineage leukemia 3/4 complexes. Stimulation with retinoic acid leads to the recruitment of UTX-containing complexes to HOX genes, which results in demethylation of histone H3 lysine 27 and concomitant methylation of histo...
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todo:paper_02707306_v34_n19_p3765_RochaViegas2023-10-03T15:14:51Z Role of UTX in retinoic acid receptor-mediated gene regulation in leukemia Rocha-Viegas, L. Villa, R. Gutierrez, A. Iriondo, O. Shiekhattar, R. Croce, L.D. histone H3 lysine protein retinoic acid retinoic acid receptor alpha unclassified drug utx protein antineoplastic agent ASH2L protein, human DNA binding protein histone histone demethylase nuclear protein retinoic acid retinoic acid receptor retinoic acid receptor alpha transcription factor UTX protein, human Article cell differentiation cell maturation chromatin immunoprecipitation controlled study flow cytometry fluorescence activated cell sorting gene activation gene control gene expression gene overexpression gene silencing gene targeting genetic transcription genetic transfection human human cell immunoprecipitation in vivo study promoter region promyelocytic leukemia protein depletion protein interaction quantitative analysis retrovirus infection reverse transcription polymerase chain reaction transcription initiation U937 cell line article drug effect gene expression regulation genetics HEK293 cell line leukemia metabolism pathology tumor cell line Antineoplastic Agents Cell Differentiation Cell Line, Tumor DNA-Binding Proteins Gene Expression Regulation, Neoplastic Gene Knockdown Techniques HEK293 Cells Histone Demethylases Histones Humans Leukemia Nuclear Proteins Promoter Regions, Genetic Receptors, Retinoic Acid Transcription Factors Tretinoin U937 Cells Human UTX, a member of the Jumonji C family of proteins, associates with mixed-lineage leukemia 3/4 complexes. Stimulation with retinoic acid leads to the recruitment of UTX-containing complexes to HOX genes, which results in demethylation of histone H3 lysine 27 and concomitant methylation of histone H3 lysine 4. Here, we show that UTX interacts with the retinoic acid receptor α (RARα) and that this interaction is essential for proper differentiation of leukemic U937 cells in response to retinoic acid. UTX occupies the promoters of several RAR target genes and regulates their transcriptional output by modulating ASH2L complex recruitment. Overexpression of UTX in promyelocytic NB4 cells results in enhanced cellular differentiation upon retinoic acid treatment. Our results show that UTX is important for RAR-mediated transcription and provide insight into the critical role of cross talk between histone H3 lysine 4 methylation and histone H3 lysine 27 demethylation during cellular differentiation. © 2014, American Society for Microbiology. Fil:Rocha-Viegas, L. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_02707306_v34_n19_p3765_RochaViegas |
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Universidad de Buenos Aires |
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I-28 |
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R-134 |
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Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
histone H3 lysine protein retinoic acid retinoic acid receptor alpha unclassified drug utx protein antineoplastic agent ASH2L protein, human DNA binding protein histone histone demethylase nuclear protein retinoic acid retinoic acid receptor retinoic acid receptor alpha transcription factor UTX protein, human Article cell differentiation cell maturation chromatin immunoprecipitation controlled study flow cytometry fluorescence activated cell sorting gene activation gene control gene expression gene overexpression gene silencing gene targeting genetic transcription genetic transfection human human cell immunoprecipitation in vivo study promoter region promyelocytic leukemia protein depletion protein interaction quantitative analysis retrovirus infection reverse transcription polymerase chain reaction transcription initiation U937 cell line article drug effect gene expression regulation genetics HEK293 cell line leukemia metabolism pathology tumor cell line Antineoplastic Agents Cell Differentiation Cell Line, Tumor DNA-Binding Proteins Gene Expression Regulation, Neoplastic Gene Knockdown Techniques HEK293 Cells Histone Demethylases Histones Humans Leukemia Nuclear Proteins Promoter Regions, Genetic Receptors, Retinoic Acid Transcription Factors Tretinoin U937 Cells |
| spellingShingle |
histone H3 lysine protein retinoic acid retinoic acid receptor alpha unclassified drug utx protein antineoplastic agent ASH2L protein, human DNA binding protein histone histone demethylase nuclear protein retinoic acid retinoic acid receptor retinoic acid receptor alpha transcription factor UTX protein, human Article cell differentiation cell maturation chromatin immunoprecipitation controlled study flow cytometry fluorescence activated cell sorting gene activation gene control gene expression gene overexpression gene silencing gene targeting genetic transcription genetic transfection human human cell immunoprecipitation in vivo study promoter region promyelocytic leukemia protein depletion protein interaction quantitative analysis retrovirus infection reverse transcription polymerase chain reaction transcription initiation U937 cell line article drug effect gene expression regulation genetics HEK293 cell line leukemia metabolism pathology tumor cell line Antineoplastic Agents Cell Differentiation Cell Line, Tumor DNA-Binding Proteins Gene Expression Regulation, Neoplastic Gene Knockdown Techniques HEK293 Cells Histone Demethylases Histones Humans Leukemia Nuclear Proteins Promoter Regions, Genetic Receptors, Retinoic Acid Transcription Factors Tretinoin U937 Cells Rocha-Viegas, L. Villa, R. Gutierrez, A. Iriondo, O. Shiekhattar, R. Croce, L.D. Role of UTX in retinoic acid receptor-mediated gene regulation in leukemia |
| topic_facet |
histone H3 lysine protein retinoic acid retinoic acid receptor alpha unclassified drug utx protein antineoplastic agent ASH2L protein, human DNA binding protein histone histone demethylase nuclear protein retinoic acid retinoic acid receptor retinoic acid receptor alpha transcription factor UTX protein, human Article cell differentiation cell maturation chromatin immunoprecipitation controlled study flow cytometry fluorescence activated cell sorting gene activation gene control gene expression gene overexpression gene silencing gene targeting genetic transcription genetic transfection human human cell immunoprecipitation in vivo study promoter region promyelocytic leukemia protein depletion protein interaction quantitative analysis retrovirus infection reverse transcription polymerase chain reaction transcription initiation U937 cell line article drug effect gene expression regulation genetics HEK293 cell line leukemia metabolism pathology tumor cell line Antineoplastic Agents Cell Differentiation Cell Line, Tumor DNA-Binding Proteins Gene Expression Regulation, Neoplastic Gene Knockdown Techniques HEK293 Cells Histone Demethylases Histones Humans Leukemia Nuclear Proteins Promoter Regions, Genetic Receptors, Retinoic Acid Transcription Factors Tretinoin U937 Cells |
| description |
Human UTX, a member of the Jumonji C family of proteins, associates with mixed-lineage leukemia 3/4 complexes. Stimulation with retinoic acid leads to the recruitment of UTX-containing complexes to HOX genes, which results in demethylation of histone H3 lysine 27 and concomitant methylation of histone H3 lysine 4. Here, we show that UTX interacts with the retinoic acid receptor α (RARα) and that this interaction is essential for proper differentiation of leukemic U937 cells in response to retinoic acid. UTX occupies the promoters of several RAR target genes and regulates their transcriptional output by modulating ASH2L complex recruitment. Overexpression of UTX in promyelocytic NB4 cells results in enhanced cellular differentiation upon retinoic acid treatment. Our results show that UTX is important for RAR-mediated transcription and provide insight into the critical role of cross talk between histone H3 lysine 4 methylation and histone H3 lysine 27 demethylation during cellular differentiation. © 2014, American Society for Microbiology. |
| format |
JOUR |
| author |
Rocha-Viegas, L. Villa, R. Gutierrez, A. Iriondo, O. Shiekhattar, R. Croce, L.D. |
| author_facet |
Rocha-Viegas, L. Villa, R. Gutierrez, A. Iriondo, O. Shiekhattar, R. Croce, L.D. |
| author_sort |
Rocha-Viegas, L. |
| title |
Role of UTX in retinoic acid receptor-mediated gene regulation in leukemia |
| title_short |
Role of UTX in retinoic acid receptor-mediated gene regulation in leukemia |
| title_full |
Role of UTX in retinoic acid receptor-mediated gene regulation in leukemia |
| title_fullStr |
Role of UTX in retinoic acid receptor-mediated gene regulation in leukemia |
| title_full_unstemmed |
Role of UTX in retinoic acid receptor-mediated gene regulation in leukemia |
| title_sort |
role of utx in retinoic acid receptor-mediated gene regulation in leukemia |
| url |
http://hdl.handle.net/20.500.12110/paper_02707306_v34_n19_p3765_RochaViegas |
| work_keys_str_mv |
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1782031032202035200 |