Home LiteratureArticle Details
PMID: 14701874 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

SUMO modification of a novel MAR-binding protein, SATB2, modulates immunoglobulin mu gene expression.

Genes & development ·Vol. 17 ·No. 24 ·2003-12-15 ·Pages 3048-61

Dobreva G, Dambacher J, Grosschedl R

Abstract

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.

MeSH Terms
B-Lymphocytes/physiology Cell Nucleus/metabolism Chromatin/genetics,metabolism Electrophoretic Mobility Shift Assay Gene Expression Regulation Green Fluorescent Proteins Humans Immunoglobulin mu-Chains/genetics,metabolism Luminescent Proteins/metabolism Matrix Attachment Region Binding Proteins/genetics,metabolism Matrix Attachment Regions Molecular Sequence Data Mutation/genetics Nuclear Matrix/metabolism Plasmids Protein Inhibitors of Activated STAT Protein Transport Proteins/metabolism Small Ubiquitin-Related Modifier Proteins/physiology Transcriptional Activation Tumor Cells, Cultured
Chemicals
Chromatin Immunoglobulin mu-Chains Luminescent Proteins Matrix Attachment Region Binding Proteins Protein Inhibitors of Activated STAT Proteins Small Ubiquitin-Related Modifier Proteins Green Fluorescent Proteins
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Dobreva Gergana
Gene Center and Institute of Biochemistry, University of Munich, Munich 81377, Germany.
Dambacher Julia
Grosschedl Rudolf
References (71)
71 references, click to expand
  1. Nuclear domains.
    J Cell Sci. 2001 Aug;114(Pt 16):2891-3 PMID: 11686292
  2. A new RING for SUMO: wrestling transcriptional responses into nuclear bodies with PIAS family E3 SUMO ligases.
    Genes Dev. 2001 Dec 1;15(23):3053-8 PMID: 11731472
  3. PIASy, a nuclear matrix-associated SUMO E3 ligase, represses LEF1 activity by sequestration into nuclear bodies.
    Genes Dev. 2001 Dec 1;15(23):3088-103 PMID: 11731474
  4. The nucleoporin RanBP2 has SUMO1 E3 ligase activity.
    Cell. 2002 Jan 11;108(1):109-20 PMID: 11792325
  5. Members of the PIAS family act as SUMO ligases for c-Jun and p53 and repress p53 activity.
    Proc Natl Acad Sci U S A. 2002 Mar 5;99(5):2872-7 PMID: 11867732
  6. Subnuclear compartmentalization of immunoglobulin loci during lymphocyte development.
    Science. 2002 Apr 5;296(5565):158-62 PMID: 11935030
  7. Nuclear neighbours: the spatial and functional organization of genes and nuclear domains.
    J Cell Biochem. 1998 Aug 1;70(2):159-71 PMID: 9671222
  8. Inhibition of Stat1-mediated gene activation by PIAS1.
    Proc Natl Acad Sci U S A. 1998 Sep 1;95(18):10626-31 PMID: 9724754
  9. SUMO-1 modification of IkappaBalpha inhibits NF-kappaB activation.
    Mol Cell. 1998 Aug;2(2):233-9 PMID: 9734360
  10. Cux/CDP homeoprotein is a component of NF-muNR and represses the immunoglobulin heavy chain intronic enhancer by antagonizing the bright transcription activator.
    Mol Cell Biol. 1999 Jan;19(1):284-95 PMID: 9858552
  11. A new protease required for cell-cycle progression in yeast.
    Nature. 1999 Mar 18;398(6724):246-51 PMID: 10094048
  12. A generic protein purification method for protein complex characterization and proteome exploration.
    Nat Biotechnol. 1999 Oct;17(10):1030-2 PMID: 10504710
  13. SATB1 cleavage by caspase 6 disrupts PDZ domain-mediated dimerization, causing detachment from chromatin early in T-cell apoptosis.
    Mol Cell Biol. 2001 Aug;21(16):5591-604 PMID: 11463840
  14. The SUMO E3 ligase RanBP2 promotes modification of the HDAC4 deacetylase.
    EMBO J. 2002 Jun 3;21(11):2682-91 PMID: 12032081
  15. RAD6-dependent DNA repair is linked to modification of PCNA by ubiquitin and SUMO.
    Nature. 2002 Sep 12;419(6903):135-41 PMID: 12226657
  16. Transcription factor Sp3 is silenced through SUMO modification by PIAS1.
    EMBO J. 2002 Oct 1;21(19):5206-15 PMID: 12356736
  17. SATB1 targets chromatin remodelling to regulate genes over long distances.
    Nature. 2002 Oct 10;419(6907):641-5 PMID: 12374985
  18. Small ubiquitin-related modifier-1 (SUMO-1) modification of the glucocorticoid receptor.
    Biochem J. 2002 Nov 1;367(Pt 3):907-11 PMID: 12144530
  19. SUMO-1 modification represses Sp3 transcriptional activation and modulates its subnuclear localization.
    Mol Cell. 2002 Oct;10(4):831-42 PMID: 12419227
  20. SUMO-1 protease-1 regulates gene transcription through PML.
    Mol Cell. 2002 Oct;10(4):843-55 PMID: 12419228
  21. Regulating the regulators: lysine modifications make their mark.
    Cell. 2003 Jan 10;112(1):11-7 PMID: 12526789
  22. Modification with SUMO. A role in transcriptional regulation.
    EMBO Rep. 2003 Feb;4(2):137-42 PMID: 12612601
  23. Post-translational modification by the small ubiquitin-related modifier SUMO has big effects on transcription factor activity.
    Curr Opin Genet Dev. 2003 Apr;13(2):108-13 PMID: 12672486
  24. The polycomb protein Pc2 is a SUMO E3.
    Cell. 2003 Apr 4;113(1):127-37 PMID: 12679040
  25. Tissue-specific nuclear architecture and gene expression regulated by SATB1.
    Nat Genet. 2003 May;34(1):42-51 PMID: 12692553
  26. Opposed regulation of corepressor CtBP by SUMOylation and PDZ binding.
    Mol Cell. 2003 May;11(5):1389-96 PMID: 12769861
  27. Dynamic interplay of the SUMO and ERK pathways in regulating Elk-1 transcriptional activity.
    Mol Cell. 2003 Jul;12(1):63-74 PMID: 12887893
  28. Identification of a nuclear protein matrix.
    Biochem Biophys Res Commun. 1974 Oct 23;60(4):1410-7 PMID: 4214419
  29. Organization of the higher-order chromatin loop: specific DNA attachment sites on nuclear scaffold.
    Cell. 1984 Nov;39(1):223-32 PMID: 6091913
  30. Chromosomal loop anchorage of the kappa immunoglobulin gene occurs next to the enhancer in a region containing topoisomerase II sites.
    Cell. 1986 Jan 31;44(2):273-82 PMID: 3002631
  31. A developmental-specific factor binds to suppressor sites flanking the immunoglobulin heavy-chain enhancer.
    Genes Dev. 1989 Aug;3(8):1255-66 PMID: 2792763
  32. Immunoglobulin kappa gene expression after stable integration. II. Role of the intronic MAR and enhancer in transgenic mice.
    J Biol Chem. 1989 Dec 15;264(35):21190-5 PMID: 2512291
  33. A tissue-specific MAR/SAR DNA-binding protein with unusual binding site recognition.
    Cell. 1992 Aug 21;70(4):631-45 PMID: 1505028
  34. Characterization of SAF-A, a novel nuclear DNA binding protein from HeLa cells with high affinity for nuclear matrix/scaffold attachment DNA elements.
    EMBO J. 1992 Sep;11(9):3431-40 PMID: 1324173
  35. The immunoglobulin mu enhancer core establishes local factor access in nuclear chromatin independent of transcriptional stimulation.
    Genes Dev. 1993 Oct;7(10):2016-32 PMID: 8406005
  36. B cell-specific demethylation: a novel role for the intronic kappa chain enhancer sequence.
    Cell. 1994 Mar 11;76(5):913-23 PMID: 8124725
  37. Dependence of enhancer-mediated transcription of the immunoglobulin mu gene on nuclear matrix attachment regions.
    Science. 1994 Aug 26;265(5176):1221-5 PMID: 8066460
  38. The immunoglobulin heavy-chain matrix-associating regions are bound by Bright: a B cell-specific trans-activator that describes a new DNA-binding protein family.
    Genes Dev. 1995 Dec 15;9(24):3067-82 PMID: 8543152
  39. Intracellular receptors use a common mechanism to interpret signaling information at response elements.
    Genes Dev. 1996 May 15;10(10):1271-83 PMID: 8675013
  40. Scaffold/matrix-attached regions act upon transcription in a context-dependent manner.
    Biochemistry. 1996 Aug 27;35(34):11160-9 PMID: 8780520
  41. Extension of chromatin accessibility by nuclear matrix attachment regions.
    Nature. 1997 Jan 16;385(6613):269-72 PMID: 9000077
  42. An atypical homeodomain in SATB1 promotes specific recognition of the key structural element in a matrix attachment region.
    J Biol Chem. 1997 Apr 25;272(17):11463-70 PMID: 9111059
  43. Dynamic relocation of transcription and splicing factors dependent upon transcriptional activity.
    EMBO J. 1997 Mar 17;16(6):1401-12 PMID: 9135155
  44. Chicken MAR-binding protein ARBP is homologous to rat methyl-CpG-binding protein MeCP2.
    Mol Cell Biol. 1997 Sep;17(9):5656-66 PMID: 9271441
  45. A thymocyte factor SATB1 suppresses transcription of stably integrated matrix-attachment region-linked reporter genes.
    Biochemistry. 1997 Oct 7;36(40):12005-10 PMID: 9340009
  46. Specific inhibition of Stat3 signal transduction by PIAS3.
    Science. 1997 Dec 5;278(5344):1803-5 PMID: 9388184
  47. Conjugation with the ubiquitin-related modifier SUMO-1 regulates the partitioning of PML within the nucleus.
    EMBO J. 1998 Jan 2;17(1):61-70 PMID: 9427741
  48. The genomic sequences bound to special AT-rich sequence-binding protein 1 (SATB1) in vivo in Jurkat T cells are tightly associated with the nuclear matrix at the bases of the chromatin loops.
    J Cell Biol. 1998 Apr 20;141(2):335-48 PMID: 9548713
  49. Transcription regulation by histone methylation: interplay between different covalent modifications of the core histone tails.
    Genes Dev. 2001 Sep 15;15(18):2343-60 PMID: 11562345
  50. SUMO-1 modification activates the transcriptional response of p53.
    EMBO J. 1999 Nov 15;18(22):6455-61 PMID: 10562557
  51. Activation of p53 by conjugation to the ubiquitin-like protein SUMO-1.
    EMBO J. 1999 Nov 15;18(22):6462-71 PMID: 10562558
  52. Nuclear matrix attachment regions antagonize methylation-dependent repression of long-range enhancer-promoter interactions.
    Genes Dev. 1999 Nov 15;13(22):3003-14 PMID: 10580007
  53. MARs of antigen receptor and co-receptor genes.
    Crit Rev Eukaryot Gene Expr. 1999;9(3-4):295-310 PMID: 10651246
  54. Functional heterogeneity of small ubiquitin-related protein modifiers SUMO-1 versus SUMO-2/3.
    J Biol Chem. 2000 Mar 3;275(9):6252-8 PMID: 10692421
  55. The MAR-binding protein SATB1 orchestrates temporal and spatial expression of multiple genes during T-cell development.
    Genes Dev. 2000 Mar 1;14(5):521-35 PMID: 10716941
  56. Transcriptional augmentation: modulation of gene expression by scaffold/matrix-attached regions (S/MAR elements).
    Crit Rev Eukaryot Gene Expr. 2000;10(1):73-90 PMID: 10813396
  57. Regulation of matrix attachment region-dependent, lymphocyte-restricted transcription through differential localization within promyelocytic leukemia nuclear bodies.
    EMBO J. 2000 Aug 1;19(15):4123-33 PMID: 10921892
  58. Targeting of Ikaros to pericentromeric heterochromatin by direct DNA binding.
    Genes Dev. 2000 Sep 1;14(17):2146-60 PMID: 10970879
  59. SUMO--nonclassical ubiquitin.
    Annu Rev Cell Dev Biol. 2000;16:591-626 PMID: 11031248
  60. Matrix attachment region-dependent function of the immunoglobulin mu enhancer involves histone acetylation at a distance without changes in enhancer occupancy.
    Mol Cell Biol. 2001 Jan;21(1):196-208 PMID: 11113195
  61. Differential regulation of immunoglobulin gene transcription via nuclear matrix-associated regions.
    Cold Spring Harb Symp Quant Biol. 1999;64:109-18 PMID: 11232275
  62. SUMO, ubiquitin's mysterious cousin.
    Nat Rev Mol Cell Biol. 2001 Mar;2(3):202-10 PMID: 11265250
  63. Chromosome territories, nuclear architecture and gene regulation in mammalian cells.
    Nat Rev Genet. 2001 Apr;2(4):292-301 PMID: 11283701
  64. SUMO-1 conjugation in vivo requires both a consensus modification motif and nuclear targeting.
    J Biol Chem. 2001 Apr 20;276(16):12654-9 PMID: 11124955
  65. Sumo-1 modification regulates the DNA binding activity of heat shock transcription factor 2, a promyelocytic leukemia nuclear body associated transcription factor.
    J Biol Chem. 2001 May 25;276(21):18513-8 PMID: 11278381
  66. Transcriptional activation by a matrix associating region-binding protein. contextual requirements for the function of bright.
    J Biol Chem. 2001 Jun 15;276(24):21325-30 PMID: 11294836
  67. An E3-like factor that promotes SUMO conjugation to the yeast septins.
    Cell. 2001 Sep 21;106(6):735-44 PMID: 11572779
  68. Correlation between histone lysine methylation and developmental changes at the chicken beta-globin locus.
    Science. 2001 Sep 28;293(5539):2453-5 PMID: 11498546
  69. Involvement of PIAS1 in the sumoylation of tumor suppressor p53.
    Mol Cell. 2001 Sep;8(3):713-8 PMID: 11583632
  70. SP-RING for SUMO: new functions bloom for a ubiquitin-like protein.
    Cell. 2001 Oct 5;107(1):5-8 PMID: 11595179
  71. Regulation of heat shock transcription factor 1 by stress-induced SUMO-1 modification.
    J Biol Chem. 2001 Oct 26;276(43):40263-7 PMID: 11514557
Article Info
Journal
Genes & development
Abbr.
Genes Dev
ISSN
0890-9369
DOI
10.1101/gad.1153003
Published
2003-12-15
Pages
3048-61
Language
English
Region
United States
NLM ID
8711660
PMCID
PMC305257
Subset
IM
Databases
GENBANK
AJ606045
External Links
PubMed source DOI: 10.1101/gad.1153003 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2