Promoter 1 ofLMO2, a master gene for hematopoiesis, is regulated by the erythroid specific transcription factor GATA1

Abstract

The T cell oncogene LMO2 was first identified at the site of the translocation t(11;14)(p13;q11) in T-acute lymphocytic leukemia (T-ALL) and encodes a cysteine-rich protein with LIM-motifs. It was later shown to have an essential role in yolk sac and adult erythropoiesis. LMO2 encodes two alternative transcripts differing in the length of the 5’ untranslated region, but encoding the same protein. Transcription start site mapping revealed the 5′-end of the longer transcript, LMO2a and promoter 1. Sequencing identified two putative GATA1 sites and an overlapping SP1 site close to the transcription start site, suggesting that promoter 1 (P1) is an erythroid specific promoter. Using EMSA analysis with an oligonucleotide from promoter 1 we now show that GATA1 and SP1 bind to these sites. DNaseI hypersensitive site (DHS) mapping upstream of the transcription start site revealed four erythroid specific sites, corresponding to putative GATA1 motifs and one non-lineage specific site. Reporter gene experiments with P1 and a mutant, where both GATA sites were inactivated, showed that GATA1 plays a functional role in the erythroid specific transcriptional control of LMO2 from P1. These studies confirm that promoter 1 of the LMO2 gene is an erythroid specific promoter.