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Prepublished online as a Blood First Edition Paper on April 24, 2003; DOI 10.1182/blood-2002-11-3541.

Submitted November 21, 2002
Accepted April 16, 2003
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*
Hematopoiesis Section, National Human Genome Research Institute, Bethesda, MD, USA
National Human Genome Research Institute Transgenic Mouse Core, Bethesda, MD, USA
Rotary Bone Marrow Research Laboratory, Royal Melbourne Hospital, Melbourne, VIC, Australia
* Corresponding author; email: tedyaz{at}nhgri.nih.gov.
Hmgb3 is a member of a family of chromatin-binding proteins which 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 within hematopoietic stem cells. We inserted an IRES-GFP 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 sub-population of Lin-, c-kitHI cells that express Hmgb3. The majority of 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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