High Mobility Group A1 Chromatin Remodeling Protein Regulates Self-Renewal, Niche Formation, And Regenerative Function In Adult Stem Cells Through Wnt/Beta-Catenin Signaling

Introduction: Nuclear chromatin structure is a key determinant of stem cell function and cell fate, although factors that regulate this are only beginning to emerge. While High Mobility Group A1(HMGA1) chromatin remodeling proteins are among the most abundant, nonhistone chromatin binding proteins in adult stem cells (ASCs), their role in this setting has been unknown. HMGA1/2 proteins modulate gene expression by binding to DNA, bending chromatin, and recruiting transcription factor complexes to enhancers throughout the genome. The HMGA1 gene is highly expressed during embryogenesis with low or undetectable levels in mature, differentiated tissues. In cancer, HMGA1 re-expression occurs through oncogenic transcription factors, other epigenetic alterations, or in rare cases, chromosomal translocation events. Importantly, HMGA1 levels correlate with adverse clinical outcomes in diverse malignancies. We previously reported that Hmga1 transgenic mice develop leukemic transformation by inducing transcriptional networks involved in stem cell function and cell cycle progression.