Submitted April 18, 2007
Accepted November 20, 2007
Hls5 regulates erythroid differentiation by modulating GATA-1 activity
Raelene Endersby, Ian J. Majewski, Louise Winteringham, Jennifer G Beaumont, Amy Samuels, Robin Scaife, Esther Lim, Merlin Crossley, S. Peter Klinken*, and Jean-Philippe Lalonde
Laboratory for Cancer Medicine, Western Australian Institute for Medical Research, Centre for Medical Research, The University of Western Australia, Crawley, Australia
Division of Molecular Medicine, Walter and Eliza Hall Institute of Medical Research, Parkville, Australia
School of Molecular and Microbial Biosciences, The University of Sydney, Sydney, Australia
* Corresponding author; email: pklinken{at}waimr.uwa.edu.au.
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 upon 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 co-operatively to induce biochemical and phenotypic changes associated with erythroid/myeloid lineage switching.
