%0 Journal Article %1 Seo2005 %A Seo, Jin %A Lozano, Mary M. %A Dudley, Jaquelin P. %D 2005 %J J Biol Chem %K Animals Cell_Line,_Tumor Cell_Nucleus,_metabolism DNA,_chemistry DNA_Primers,_chemistry Dimerization Fibroblasts,_metabolism Gene_Deletion Genes,_Reporter Green_Fluorescent_Proteins,_metabolism Humans Interleukin-2_Receptor_alpha_Subunit Introns Jurkat_Cells Ligands Mammary_Glands,_Animal Mammary_Tumor_Virus,_Mouse,_genetics Matrix_Attachment_Region_Binding_Proteins,_metabolism/physiology Mice Microscopy,_Fluorescence Mutation Plasmids,_metabolism Polymerase_Chain_Reaction Promoter_Regions_(Genetics) Protein_Binding Protein_Structure,_Tertiary Proto-Oncogene_Proteins_c-myc,_metabolism RNA,_metabolism Rats Receptors,_Glucocorticoid,_metabolism Receptors,_Interleukin,_metabolism Recombinant_Fusion_Proteins,_chemistry Retroviridae,_genetics Ribonucleases,_metabolism Subcellular_Fractions Transcription,_Genetic Transfection %N 26 %P 24600-24609 %R 10.1074/jbc.M414076200 %T Nuclear matrix binding regulates SATB1-mediated transcriptional repression. %U http://dx.doi.org/10.1074/jbc.M414076200 %V 280 %X Special AT-rich binding protein 1 (SATB1) originally was identified as a protein that bound to the nuclear matrix attachment regions (MARs) of the immunoglobulin heavy chain intronic enhancer. Subsequently, SATB1 was shown to repress many genes expressed in the thymus, including interleukin-2 receptor alpha, c-myc, and those encoded by mouse mammary tumor virus (MMTV), a glucocorticoid-responsive retrovirus. SATB1 binds to MARs within the MMTV provirus to repress transcription. To address the role of the nuclear matrix in SATB1-mediated repression, a series of SATB1 deletion constructs was used to determine protein localization. Wild-type SATB1 localized to the soluble nuclear, chromatin, and nuclear matrix fractions. Mutants lacking amino acids 224-278 had a greatly diminished localization to the nuclear matrix, suggesting the presence of a nuclear matrix targeting sequence (NMTS). Transient transfection experiments showed that NMTS fusions to green fluorescent protein or LexA relocalized these proteins to the nuclear matrix. Difficulties with previous assay systems prompted us to develop retroviral vectors to assess effects of different SATB1 domains on expression of MMTV proviruses or integrated reporter genes. SATB1 overexpression repressed MMTV transcription in the presence and absence of functional glucocorticoid receptor. Repression was alleviated by deletion of the NMTS, which did not affect DNA binding, or by deletion of the MAR-binding domain. Our studies indicate that both nuclear matrix association and DNA binding are required for optimal SATB1-mediated repression of the integrated MMTV promoter and may allow insulation from cellular regulatory elements.

@article{Seo2005, abstract = {Special AT-rich binding protein 1 (SATB1) originally was identified as a protein that bound to the nuclear matrix attachment regions (MARs) of the immunoglobulin heavy chain intronic enhancer. Subsequently, SATB1 was shown to repress many genes expressed in the thymus, including interleukin-2 receptor alpha, c-myc, and those encoded by mouse mammary tumor virus (MMTV), a glucocorticoid-responsive retrovirus. SATB1 binds to MARs within the MMTV provirus to repress transcription. To address the role of the nuclear matrix in SATB1-mediated repression, a series of SATB1 deletion constructs was used to determine protein localization. Wild-type SATB1 localized to the soluble nuclear, chromatin, and nuclear matrix fractions. Mutants lacking amino acids 224-278 had a greatly diminished localization to the nuclear matrix, suggesting the presence of a nuclear matrix targeting sequence (NMTS). Transient transfection experiments showed that NMTS fusions to green fluorescent protein or LexA relocalized these proteins to the nuclear matrix. Difficulties with previous assay systems prompted us to develop retroviral vectors to assess effects of different SATB1 domains on expression of MMTV proviruses or integrated reporter genes. SATB1 overexpression repressed MMTV transcription in the presence and absence of functional glucocorticoid receptor. Repression was alleviated by deletion of the NMTS, which did not affect DNA binding, or by deletion of the MAR-binding domain. Our studies indicate that both nuclear matrix association and DNA binding are required for optimal SATB1-mediated repression of the integrated MMTV promoter and may allow insulation from cellular regulatory elements.}, added-at = {2010-01-26T20:35:53.000+0100}, author = {Seo, Jin and Lozano, Mary M. and Dudley, Jaquelin P.}, biburl = {https://www.bibsonomy.org/bibtex/21ea3489288542e849046d9f1909dbebc/denilw}, doi = {10.1074/jbc.M414076200}, file = {article:/papers/Transcription Factor Binding/SatB1/{$\Nu$}clear Matrix Binding Regulates SATB1-mediated transcriptional Repression.pdf:pdf}, institution = {Institute for Cellular and Molecular Biology, The University of Texas at Austin, Austin, Texas 78712, USA.}, interhash = {83a55a030551272f829392fb6ca32a35}, intrahash = {1ea3489288542e849046d9f1909dbebc}, journal = {J Biol Chem}, keywords = {Animals Cell_Line,_Tumor Cell_Nucleus,_metabolism DNA,_chemistry DNA_Primers,_chemistry Dimerization Fibroblasts,_metabolism Gene_Deletion Genes,_Reporter Green_Fluorescent_Proteins,_metabolism Humans Interleukin-2_Receptor_alpha_Subunit Introns Jurkat_Cells Ligands Mammary_Glands,_Animal Mammary_Tumor_Virus,_Mouse,_genetics Matrix_Attachment_Region_Binding_Proteins,_metabolism/physiology Mice Microscopy,_Fluorescence Mutation Plasmids,_metabolism Polymerase_Chain_Reaction Promoter_Regions_(Genetics) Protein_Binding Protein_Structure,_Tertiary Proto-Oncogene_Proteins_c-myc,_metabolism RNA,_metabolism Rats Receptors,_Glucocorticoid,_metabolism Receptors,_Interleukin,_metabolism Recombinant_Fusion_Proteins,_chemistry Retroviridae,_genetics Ribonucleases,_metabolism Subcellular_Fractions Transcription,_Genetic Transfection}, month = Jul, number = 26, owner = {denilw}, pages = {24600-24609}, pii = {M414076200}, pmid = {15851481}, timestamp = {2010-01-26T20:36:03.000+0100}, title = {Nuclear matrix binding regulates SATB1-mediated transcriptional repression.}, url = {http://dx.doi.org/10.1074/jbc.M414076200}, volume = 280, year = 2005 }