Multifaceted Actions of GFI1 and GFI1B in Hematopoietic Stem Cell Self-Renewal and Lineage Commitment.
Abstract
Growth factor independence 1 (GFI1) and the closely related protein GFI1B are small nuclear proteins that act as DNA binding transcriptional repressors. Both recognize the same consensus DNA binding motif via their C-terminal zinc finger domains and regulate the expression of their target genes by recruiting chromatin modifiers such as histone deacetylases (HDACs) and demethylases (LSD1) by using an N-terminal SNAG domain that comprises only 20 amino acids. The only region that is different between both proteins is the region that separates the zinc finger domains and the SNAG domain. Both proteins are co-expressed in hematopoietic stem cells (HSCs) and, to some extent, in multipotent progenitors (MPPs), but expression is specified as soon as early progenitors and show signs of lineage bias. While expression of GFI1 is maintained in lymphoid primed multipotent progenitors (LMPPs) that have the potential to differentiate into both myeloid and lymphoid cells, GFI1B expression is no longer detectable in these cells. By contrast, GFI1 expression is lost in megakaryocyte precursors (MKPs) and in megakaryocyte-erythrocyte progenitors (MEPs), which maintain a high level of GFI1B expression. Consequently, GFI1 drives myeloid and lympho...Continue Reading
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