Hls5 regulated erythroid differentiation by modulating GATA-1 activity

Hemopoietic lineage switch (His) 5 and 7 were originally isolated as genes upregulated during an erythroid-to-myeloid lineage switch. We have shown previously that HIs7/Mlf1 imposes a monoblastoid phenotype on erythroleukemic cells. Here we show that Hls5 impedes erythroid maturation by restricting proliferation and inhibiting hemoglobin synthesis; however, HIs5 does not influence the morphology of erythroid cells. Under the influence of GATA-1, HIs5 relocates from cytoplasmic granules to the nucleus where it associates with both FOG-1 and GATA-1. In the nucleus, HIs5 is able to suppress GATA-1-mediated transactivation and reduce GATA-1 binding to DNA. We conclude that HIs5 and Hls7/Mlf1 act cooperatively to induce biochemical and phenotypic changes associated with erythroid/myeloid lineage switching.