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Prepublished online as a Blood First Edition Paper on December 12, 2002; DOI 10.1182/blood-2002-09-2924.

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Submitted September 25, 2002
Accepted November 27, 2002

Regulation of human {beta}2-microglobulin transactivation in hematopoietic cells

Sam J Gobin*, Paula Biesta, and Peter J Van den Elsen

Immunohematology and Blood Transfusion, Leiden University Medical Center (LUMC), Leiden, The Netherlands

* Corresponding author; email: gobin{at}lumc.nl.

{beta}2-microglobulin ({beta}2m) is a chaperone of major histocompatibility complex (MHC) class I (-like) molecules that play a central role in antigen presentation, immunoglobulin transport and iron metabolism. It is therefore of importance that {beta}2m is adequately expressed in cells that perform these functions, such as hematopoietic cells. In this study we investigated the transcriptional regulation of {beta}2m in lymphoid and myeloid cell lines through a promoter containing a putative E box, Ets/interferon-stimulated response element (ISRE) and {kappa}B site. Here we show that USF1 and USF2 bind to the E box and regulate {beta}2m transactivation. The nuclear factor {kappa}B (NF-{kappa}B) subunits p50 and p65 bind to the {kappa}B box and p65 transactivates {beta}2m. Interferon regulatory factor 1 (IRF1), IRF2, IRF4 and IRF8, but not PU.1, bind to the ISRE and IRF1 and IRF3 are strong transactivators of b2m. Together, all three boxes are important for the constitutive and cytokine-induced levels of {beta}2m expression in lymphoid and myeloid cell types. As such, b2m transactivation is under the control of important transcriptional pathways, which are activated during injury, infection and inflammation.


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