title: The gata1/pu.1 lineage fate paradigm varies between blood populations and is modulated by tif1γ.
abstract: Lineage fate decisions underpin much of development as well as tissue homeostasis in the adult. A mechanistic paradigm for such decisions is the erythroid versus myeloid fate decision controlled by cross-antagonism between gata1 and pu.1 transcription factors. In this study, we have systematically tested this paradigm in blood-producing populations in zebrafish embryos, including the haematopoietic stem cells (HSCs), and found that it takes a different form in each population. In particular, gata1 activity varies from autostimulation to autorepression. In addition, we have added a third member to this regulatory kernel, tif1γ (transcription intermediate factor-1γ). We show that tif1γ modulates the erythroid versus myeloid fate outcomes from HSCs by differentially controlling the levels of gata1 and pu.1. By contrast, tif1γ positively regulates both gata1 and pu.1 in primitive erythroid and prodefinitive erythromyeloid progenitors. We therefore conclude that the gata1/pu.1 paradigm for lineage decisions takes different forms in different cellular contexts and is modulated by tif1γ.
authors.affiliation: Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford University, Oxford, UK.
authors.forename: Rui
authors.initials: R
authors.lastname: Monteiro
authors.forename: Claire
authors.initials: C
authors.lastname: Pouget
authors.forename: Roger
authors.initials: R
authors.lastname: Patient
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D004625:Embryo, Nonmammalian; D050982:GATA1 Transcription Factor / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D006412:Hematopoietic Stem Cells / Q000502:physiology; D009687:Nuclear Proteins / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D015534:Trans-Activators / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000378:metabolism*; D000099232:Proto-Oncogene Protein Spi-1
chemical_list: D050982:GATA1 Transcription Factor; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D029961:Zebrafish Proteins; D000099232:Proto-Oncogene Protein Spi-1; C494691:gata1a protein, zebrafish; C093517:transcriptional intermediary factor 1