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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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Blood, 15 April 2003, Vol. 101, No. 8, pp. 3058-3064
IMMUNOBIOLOGY
Regulation of human  2-microglobulin
transactivation in hematopoietic cells
Sam J. P. Gobin,
Paula Biesta, and
Peter J. Van den
Elsen
From the Department of Immunohematology and Blood
Transfusion, Leiden University Medical Center, Leiden, the
Netherlands.
 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 upstream stimulatory factor 1 (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 Ets/ISRE, and IRF1 and IRF3 are
strong transactivators of 2m. Together, all 3 boxes are
important for the constitutive and cytokine-induced levels of
2m expression in lymphoid and myeloid cell types. As such, 2m transactivation is under the control of
important transcriptional pathways, which are activated during injury,
infection, and inflammation.
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