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, David M. Bodine

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73 Citations (Scopus)

Abstract

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-7Rα- cells, and Ter119+ erythroid cells. We observed that long-term repopulating ability is entirely contained in the subpopulation of Lin -, c-kitH1 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.

Original languageEnglish
Pages (from-to)1298-1306
Number of pages9
JournalBlood
Volume102
Issue number4
DOIs
Publication statusPublished - 15 Aug 2003
Externally publishedYes

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