MLLT3 regulates early human erythroid and megakaryocytic cell fate.
Regulatory mechanisms of human hematopoiesis remain largely uncharacterized. Through expression profiling of prospectively isolated stem and primitive progenitor cells as well as committed progenitors from cord blood (CB), we identified MLLT3 as a candidate regulator of erythroid/megakaryocytic (E/Meg) lineage decisions. Through the analysis of the hematopoietic potential of primitive cord blood cells in which MLLT3 expression has been knocked down, we identify a requirement for MLLT3 in the elaboration of the erythroid and megakaryocytic lineages. Conversely, forced expression of MLLT3 promotes the output of erythroid and megakaryocytic progenitors, and analysis of MLLT3 mutants suggests that this capacity of MLLT3 depends on its transcriptional regulatory activity. Gene expression and cis-regulatory element analyses reveal crossregulatory interactions between MLLT3 and E/Meg-affiliated transcription factor GATA-1. Taken together, the data identify MLLT3 as a regulator of early erythroid and megakaryocytic cell fate in the human system.
Pina
Cristina
C
MRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, UK.
May
Gillian
G
Soneji
Shamit
S
Hong
Dengli
D
Enver
Tariq
T
D002478:Cells, Cultured; D004920:Erythropoiesis / Q000502:physiology*; D005312:Fetal Blood / Q000166:cytology / Q000378:metabolism*; D050982:GATA1 Transcription Factor / Q000235:genetics / Q000378:metabolism; D020868:Gene Silencing; D006801:Humans; D008533:Megakaryocytes / Q000166:cytology / Q000378:metabolism*; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D020218:Response Elements / Q000502:physiology; D034061:Thrombopoiesis / Q000502:physiology*
D050982:GATA1 Transcription Factor; C494688:GATA1 protein, human; C489901:MLLT3 protein, human; D009687:Nuclear Proteins