Hmgb3: an HMG-box family member expressed in primitive hematopoietic cells that inhibits myeloid and B-cell differentiation.
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-7Ralpha- 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.
Nemeth
Michael J
MJ
Hematopoiesis Section, National Human Genome Research Institute, Bethesda, MD 20892-4442, USA.
Curtis
David J
DJ
Kirby
Martha R
MR
Garrett-Beal
Lisa J
LJ
Seidel
Nancy E
NE
Cline
Amanda P
AP
Bodine
David M
DM
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology; D018076:DNA, Complementary / Q000235:genetics; D015536:Down-Regulation; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000235:genetics; D025765:HMGB3 Protein / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D006410:Hematopoiesis / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D023461:Myeloid Progenitor Cells / Q000166:cytology / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012190:Retroviridae / Q000235:genetics; D019089:Stem Cell Factor / Q000032:analysis
D018076:DNA, Complementary; D025765:HMGB3 Protein; D012333:RNA, Messenger; D019089:Stem Cell Factor