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...

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Bibliographic Details
Published in:Blood 2008-02, Vol.111 (4), p.1946-1950
Main Authors: Endersby, Raelene, Majewski, Ian J., Winteringham, Louise, Beaumont, Jennifer G., Samuels, Amy, Scaife, Robin, Lim, Esther, Crossley, Merlin, Klinken, S. Peter, Lalonde, Jean-Philippe
Format: Article
Language:English
Subjects:
Apoptosis Regulatory Proteins - physiology
Biological and medical sciences
Cell Cycle
Cell Differentiation - drug effects
Cell Differentiation - physiology
Cell Line
Cell Line, Tumor
DNA Primers
Erythropoietin - pharmacology
GATA1 Transcription Factor - physiology
Globins - genetics
Hematologic and hematopoietic diseases
Humans
Leukemia, Erythroblastic, Acute
Medical sciences
Nuclear Proteins - physiology
Transcription Factors - physiology
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Summary: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.
ISSN:0006-4971
1528-0020
DOI:10.1182/blood-2007-04-085746