SUMO modification of a novel MAR-binding protein, SATB2, modulates immunoglobulin mu gene expression.
Nuclear matrix attachment regions (MARs) are regulatory DNA sequences that are important for higher-order chromatin organization, long-range enhancer function, and extension of chromatin modifications. Here we characterize a novel cell type-specific MAR-binding protein, SATB2, which binds to the MARs of the endogenous immunoglobulin micro locus in pre-B cells and enhances gene expression. We found that SATB2 differs from the closely related thymocyte-specific protein SATB1 by modifications of two lysines with the small ubiquitive related modifier (SUMO), which are augmented specifically by the SUMO E3 ligase PIAS1. Mutations of the SUMO conjugation sites of SATB2 enhance its activation potential and association with endogenous MARs in vivo, whereas N-terminal fusions with SUMO1 or SUMO3 decrease SATB2-mediated gene activation. Sumoylation is also involved in targeting SATB2 to the nuclear periphery, raising the possibility that this reversible modification of a MAR-binding protein may contribute to the modulation of subnuclear DNA localization.
Dobreva
Gergana
G
Gene Center and Institute of Biochemistry, University of Munich, Munich 81377, Germany.
Dambacher
Julia
J
Grosschedl
Rudolf
R
D001402:B-Lymphocytes / Q000502:physiology; D002467:Cell Nucleus / Q000378:metabolism; D002843:Chromatin / Q000235:genetics / Q000378:metabolism; D024202:Electrophoretic Mobility Shift Assay; D005786:Gene Expression Regulation; D049452:Green Fluorescent Proteins; D006801:Humans; D007148:Immunoglobulin mu-Chains / Q000235:genetics* / Q000378:metabolism; D008164:Luminescent Proteins / Q000378:metabolism; D036961:Matrix Attachment Region Binding Proteins / Q000235:genetics* / Q000378:metabolism; D045170:Matrix Attachment Regions; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D015530:Nuclear Matrix / Q000378:metabolism*; D010957:Plasmids; D050828:Protein Inhibitors of Activated STAT; D021381:Protein Transport; D011506:Proteins / Q000378:metabolism; D025841:Small Ubiquitin-Related Modifier Proteins / Q000502:physiology*; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured
D002843:Chromatin; D007148:Immunoglobulin mu-Chains; D008164:Luminescent Proteins; D036961:Matrix Attachment Region Binding Proteins; D050828:Protein Inhibitors of Activated STAT; D011506:Proteins; D025841:Small Ubiquitin-Related Modifier Proteins; D049452:Green Fluorescent Proteins