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

Submitted September 25, 2002
Accepted November 27, 2002
Regulation of human 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.
2-microglobulin ( 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 2m is adequately expressed in cells that perform these functions, such as hematopoietic cells. In this study we investigated the transcriptional regulation of 2m in lymphoid and myeloid cell lines through a promoter containing a putative E box, Ets/interferon-stimulated response element (ISRE) and B site. Here we show that USF1 and USF2 bind to the E box and regulate 2m transactivation. The nuclear factor B (NF- B) subunits p50 and p65 bind to the B box and p65 transactivates 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 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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