Hmgb2 Is a Novel Transcriptional Regulator of Latexin in Hematopoietic Stem Cells

Hematopoietic stem cells (HSCs) provide life-long production of blood cells and undergo self-renewal division in order to sustain the stem cell pool. Precisely regulated HSC pool maintenance and blood cell production is vital for organismal survival. We previously have identified a protein, latexin (Lxn), as a novel regulator of HSCs in mice, whose natural variation in the expression is inversely correlated with HSC population size. However, the molecular mechanisms involved in transcriptional regulation of Lxn in HSCs have not been clearly defined. By using DNA pull down and mass spectrometry, we identified several proteins that bind to the promoter region of Lxn. One top candidate is Hmgb2(High mobility group protein B2). ChIP Q-PCR assay and luciferase assay confirmed the binding of Hmgb2 to Lxn promoter with the potential role of transcriptional repressor. We also found that knock-down of Hmgb2 increases the endogenous Lxn expression at both mRNA and protein levels in hematopoietic cell line EML cells and primary HSC cells. As a result, HSC number was demonstrated decreased in vitro and in vivo due to decreased self-renewal and proliferation and increased apoptosis. This study, for the first time, revealed the transcriptional regulation of Lxn by Hmgb2.