Differential Regulation of Immunoglobulin Gene Transcription via Nuclear Matrix-associated Regions
- C. WEBB,
- R.-T. ZONG,
- D. LIN,
- Z. WANG,
- M. KAPLAN,
- Y. PAULIN,
- E. SMITH,
- L. PROBST,
- J. BRYANT,
- A. GOLDSTEIN,
- R. SCHEUERMANN, and
- P. TUCKER
- *Department of Immunobiology and Cancer, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma 73104; †Institution for Cellular and Molecular Biology, Department of Molecular Genetics and Microbiology, University of Texas at Austin, Austin, Texas 78712-1095; ‡Walther Oncology Center, University of Indiana Medical School, Indianapolis, Indiana 46202;§Department of Pathology, University of Texas Southwestern Medical Center, Dallas, Texas 75235-9072
This extract was created in the absence of an abstract.
Excerpt
We have identified a nuclear-matrix-associated, Bcell-restricted regulator of IgH transcription (Bright)(Herrscher et al. 1995). Bright binds and trans-activatesvia specific A/T-rich sequences (MARs) within and necessary for nuclear matrix attachment of the IgH intronicenhancer (Eµ). We have found that a previously identified protein, Cux/CDP, which resides within matrices ofnon-B and early lineage-B (pre-B) cells, represses Eµ viathe same binding sites bound by Bright in more differentiated B cells (Wang et al. 1999). Cux can effectively antagonize Bright binding and trans-activation and appearsto comprise (at least in part) a previously identified protein/DNA complex, NF-µNR (nuclear factor implicatedin µ IgH negative regulation) (Scheuermann and Chen1989). We hypothesize that the reciprocal action of thesefactors contributes to the cell-type-restricted on/off stateof Eµ and to the increase in Eµ activity during B-cell lineage development/differentiation. We suggest that anovel and potentially rate-limiting consequence is toswitch the balance of IgH nuclear matrix attachment.Here, we discuss the structure, function, and expressionof Bright, Cux/CDP, and molecules that interact withthem in the context of this model...
