This is the author accepted manuscript. It is currently under an indefinite embargo pending publication of the final version. ; Lim domain only 2 (LMO2) is a transcriptional co-factor required for angiogenesis and the specification of haematopoietic cells during development. LMO2 is widely expressed within haematopoiesis with the exception of T-cells. Failure to downregulate LMO2 during T-cell maturation leads to leukaemia, thus underlining the critical nature of context-dependent regulation of LMO2 expression. We previously identified a distal regulatory element of LMO2 (element -25) that cooperates with the proximal promoter in directing haematopoietic expression. Here we dissected the functional activity of element -25 and showed it to consist of two modules that conferred independent and cell-type specific activities: a 3? myeloid enhancer and a 5? T-cell repressor. The myeloid enhancer was bound by GATA2 in progenitors and its activity depended on a highly conserved GATA motif, whereas the T-cell repressor moiety of element -25 was bound by the Core Binding Factor in T-cells and its repressive activity depended on a highly conserved RUNT motif. Since the myeloid enhancer and nearby downstream region is recurrently involved in oncogenic translocations, our data suggest that the -25 enhancer region provides an open chromatin environment prone to translocations, which in turn cause aberrant LMO2 expression in T-cells due to the removal of the adjacent T-cell repressor. ; This work was supported by Leukaemia and Lymphoma Research (BG) (http://leukaemialymphomaresearch.org.uk/, grants number 07060 and 12029), a fellowship from the Swiss National Science Foundation (NB) (http://www.snf.ch/) and Wellcome Trust Infrastructure support funding for the Cambridge Institute for Medical Research ((http://www.wellcome.ac.uk/) grant number 100140/Z/12/Z) and the Wellcome Trust and MRC Cambridge Stem Cell Institute (http://www.mrc.ac.uk/, grant number 097922/Z/11/Z).