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Prepublished online as a Blood First Edition Paper on April 24, 2003; DOI 10.1182/blood-2002-11-3541.
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Blood, 15 August 2003, Vol. 102, No. 4, pp. 1298-1306
HEMATOPOIESIS
Hmgb3: an HMG-box family member expressed in primitive hematopoietic cells that inhibits myeloid and B-cell differentiation
Michael J. Nemeth,
David J. Curtis,
Martha R. Kirby,
Lisa J. Garrett-Beal,
Nancy E. Seidel,
Amanda P. Cline, and
David M. Bodine
From the Hematopoiesis Section, National Human Genome Research Institute, Bethesda, MD, and the National Human Genome Research Institute Transgenic Mouse Core.
Hmgb3 is a member of a family of chromatin-binding proteins that can alter DNA structure to facilitate transcription factor binding. We identified the Hmgb3 cDNA in a subtractive hybridization screen for transcripts that are preferentially expressed in hematopoietic stem cells. We inserted an internal ribosomal entry site–green fluorescence protein cassette into the 3' untranslated region of the X-linked Hmgb3 locus to identify Hmgb3-expressing cells. In adult mice, Hmgb3 mRNA is detected in bone marrow cells, primitive Lin–, c-kit+, Sca-1+, IL-7R – cells, and Ter119+ erythroid cells. We observed that long-term repopulating ability is entirely contained in the subpopulation of Lin–, c-kitHI cells that express Hmgb3. Most common lymphoid and myeloid progenitors express Hmgb3. Introduction of a retrovirus containing the Hmgb3 cDNA into mouse bone marrow stem cells demonstrated that enforced expression of Hmgb3 inhibited B-cell and myeloid differentiation. We conclude that down-regulation of Hmgb3 protein levels is an important step for myeloid and B-cell differentiation.
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