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The transcription factors that control lineage specification of haematopoietic stem cells (HSCs) have been well described for the myeloid and lymphoid lineages, whereas transcriptional control of erythroid (E) and megakaryocytic (Mk) fate is less understood. We here use conditional removal of the GATA-1 and FOG-1 transcription factors to identify FOG-1 as required for the formation of all committed Mk- and E-lineage progenitors, whereas GATA-1 was observed to be specifically required for E-lineage commitment. FOG-1-deficient HSCs and preMegEs, the latter normally bipotent for the Mk and E lineages, underwent myeloid transcriptional reprogramming, and formed myeloid, but not erythroid and megakaryocytic cells in vitro. These results identify FOG-1 and GATA-1 as required for formation of bipotent Mk/E progenitors and their E-lineage commitment, respectively, and show that FOG-1 mediates transcriptional Mk/E programming of HSCs as well as their subsequent Mk/E-lineage commitment. Finally, C/EBPs and FOG-1 exhibited transcriptional cross-regulation in early myelo-erythroid progenitors making their functional antagonism a potential mechanism for separation of the myeloid and Mk/E lineages.

Original publication

DOI

10.1038/emboj.2011.390

Type

Journal article

Journal

EMBO J

Publication Date

18/01/2012

Volume

31

Pages

351 - 365

Keywords

Animals, Bone Marrow Cells, CCAAT-Enhancer-Binding Protein-beta, CCAAT-Enhancer-Binding Proteins, Cell Lineage, Cells, Cultured, Colony-Forming Units Assay, Erythroid Precursor Cells, Erythropoiesis, GATA1 Transcription Factor, Gene Expression Regulation, Developmental, Megakaryocyte Progenitor Cells, Megakaryocyte-Erythroid Progenitor Cells, Mice, Mice, Transgenic, Nuclear Proteins, Thrombopoiesis, Transcription Factors, Transcription, Genetic