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PMID: 10921892 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Regulation of matrix attachment region-dependent, lymphocyte-restricted transcription through differential localization within promyelocytic leukemia nuclear bodies.

The EMBO journal ·Vol. 19 ·No. 15 ·2000-08-01 ·Pages 4123-33

Zong RT, Das C, Tucker PW

Abstract

Bright (B cell regulator of IgH transcription) transactivates the immunoglobulin heavy chain (IgH) intronic enhancer, Emicro, by binding to matrix attachment regions (MARs), sites necessary for DNA attachment to the nuclear matrix. Here we report that Bright interacts with the ubiquitous autoantigen Sp100, a component of promyelocytic leukemia nuclear bodies (PML NBs), and with LYSp100B/Sp140, the lymphoid-restricted homolog of Sp100. Both in intact cells and in nuclear matrix preparations, the majority of Bright and Sp100 colocalize within PML NBs. In contrast, Bright colocalizes with only a small fraction of LYSp100B while inducing a redistribution of the majority of LYSp100B from its associated nuclear domains (LANDs) into nucleoplasm and cytoplasm. Sp100 represses the MAR-binding and transactivation activity of Bright. LYSp100B interacts more weakly with Bright but requires significantly higher levels than Sp100 to inhibit MAR binding. However, it strongly stimulates Bright transactivation through E mu. We suggest that Sp100 and LYSp100B interactions with Bright have different consequences for IgH transcription, potentially through differential association of E mu MARs with nuclear matrix- associated PML NBs and LANDs.

MeSH Terms
Antigens, Nuclear Autoantigens/metabolism Cell Compartmentation Cell Nucleus/ultrastructure DNA-Binding Proteins/metabolism Fluorescent Antibody Technique Humans Immunoglobulin Heavy Chains/genetics Leukemia, Promyelocytic, Acute Molecular Sequence Data Nuclear Matrix Nuclear Proteins/metabolism Oncogenes Protein Binding Trans-Activators/metabolism Transcription Factors Transcriptional Activation Tumor Cells, Cultured Two-Hybrid System Techniques
Chemicals
ARID3A protein, human Antigens, Nuclear Autoantigens DNA-Binding Proteins Immunoglobulin Heavy Chains Nuclear Proteins Trans-Activators Transcription Factors Sp100 protein, human
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Zong R T
Department of Molecular Genetics and The Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, TX 78712, USA.
Das C
Tucker P W
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
DOI
10.1093/emboj/19.15.4123
Published
2000-08-01
Pages
4123-33
Language
English
Region
England
NLM ID
8208664
PMCID
PMC306587
Subset
IM
Databases
GENBANK
U60335
External Links
PubMed source DOI: 10.1093/emboj/19.15.4123 PMC Full Text View journal details
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