Hls5 regulated erythroid differentiation by modulating GATA-1 activity.
Hemopoietic lineage switch (Hls) 5 and 7 were originally isolated as genes up-regulated during an erythroid-to-myeloid lineage switch. We have shown previously that Hls7/Mlf1 imposes a monoblastoid phenotype on erythroleukemic cells. Here we show that Hls5 impedes erythroid maturation by restricting proliferation and inhibiting hemoglobin synthesis; however, Hls5 does not influence the morphology of erythroid cells. Under the influence of GATA-1, Hls5 relocates from cytoplasmic granules to the nucleus where it associates with both FOG-1 and GATA-1. In the nucleus, Hls5 is able to suppress GATA-1-mediated transactivation and reduce GATA-1 binding to DNA. We conclude that Hls5 and Hls7/Mlf1 act cooperatively to induce biochemical and phenotypic changes associated with erythroid/myeloid lineage switching.
Laboratory for Cancer Medicine, Western Australian Institute for Medical Research, Centre for Medical Research, University of Western Australia, Crawley, Australia.
Raelene
R
Endersby
Ian J
IJ
Majewski
Louise
L
Winteringham
Jennifer G
JG
Beaumont
Amy
A
Samuels
Robin
R
Scaife
Esther
E
Lim
Merlin
M
Crossley
S Peter
SP
Klinken
Jean-Philippe
JP
Lalonde
D051017:Apoptosis Regulatory Proteins / Q000502:physiology*; D002453:Cell Cycle; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002460:Cell Line; D045744:Cell Line, Tumor; D017931:DNA Primers; D004921:Erythropoietin / Q000494:pharmacology; D050982:GATA1 Transcription Factor / Q000502:physiology*; D005914:Globins / Q000235:genetics; D006801:Humans; D004915:Leukemia, Erythroblastic, Acute; D009687:Nuclear Proteins / Q000502:physiology; D014157:Transcription Factors / Q000502:physiology
D051017:Apoptosis Regulatory Proteins; D017931:DNA Primers; D050982:GATA1 Transcription Factor; C494688:GATA1 protein, human; D009687:Nuclear Proteins; C476418:TRIM35 protein, human; D014157:Transcription Factors; C498432:ZFPM1 protein, human; D004921:Erythropoietin; D005914:Globins