Although WT and Lmo2 −/− ES cells have a similar capacity to produce Flk-1 + cells , our experiments showed that LMO2 exerts its function already at the HB stage by positioning the LMO2 complex to regulatory elements important for the establishment of the haematopoietic program . As the peaks identified by the three - way overlap of the LMO2 , TAL1 and LDB1 ChIPseq data were the sites with the highest number of reads in each of the independent samples , we conclude that these regulatory elements   Table showing the number of genes associated with LMO2 ChIPseq peaks that have increased or decreased expression ( > 4 - fold ) in WT compared to Lmo2 −/− cells . ( D ) Heat map of hierarchically clustered genes that associate with common TAL1 , LMO2 and LDB1 ChIPseq peaks . These genes are either the nearest 5 or 3 gene , or contain the peak within the gene body . Scale bar represents colour index for the log 2 FPKM values . Self - organizing tree analysis identified three clusters , which are numbered 1 to 3 . exhibit the highest affinity for this complex . In the absence of LMO2 , binding of TAL1 only remained at the strongest of these binding sites , albeit at a lower level , whereas the majority of TAL1 binding was found at novel binding sites . It has previously been shown that the interaction of LMO2 with TAL1 directly increases the stability of TAL1 / E2A heterodimer ( 57 ) . Experiments with TAL1 DNA - binding deficient mutants showed that DNA - binding activity of TAL1 was dispensable for specification of haematopoietic development ( 53 ) , only when the interaction of the TAL1 HLH domain with LMO2 was retained ( 57 ) . In addition , in the presence of LMO2 , TAL1 could associate with chromatin in the absence of its DNA binding domain , albeit with a lower affinity ( 58 ) . Our motif analysis of the threeway overlap of LMO2 , TAL1 and LDB1 ChIP indicated a very strong enrichment of GATA binding motifs ( Figure 5 ) . Taken together , this indicates that the interaction through LMO2 plays an important role in directing TAL1 to the correct binding sites , whereas without LMO2 , TAL1 has lower DNA binding activity and specificity . Comparison of our data to previously published LDB-1 ChIPseq data in Flk-1 + cells ( 28 ) and in Lin − bone marrow ( 59 ) showed that the overlap is particularly enriched for those LDB1 peaks that are part of the three - way overlap ( 83 % and 51 % of LMO2 , TAL1 and LDB1 ChIP peaks respectively ) . In addition , our and previous studies identify the same list of target genes ( e.g. Tal1 , Gata2 , Runx1 , Lmo2 , Runx2t2 and Sox7 ) . Intersecting the lists of differentially expressed genes reported by Mylona et al . indicated that the Ldb1 −/− was more similar to the Tal1 −/− , in line with the developmental block occurring earlier than in the Lmo2 −/− . Meta - analysis of the LMO2 complex binding sites identified an overrepresentation of regulatory elements important for haematopoietic development . These included transcription factor genes known to be important at the HB stage ( e.g. Fli1 ( 52,59 ) , Gata2 ( 32 ) , Erg ( 55 ) ) , genes that are important for the HE and endothelial - haematopoietic transition ( e.g. Gfi1 ( 60 ) ) , those with known haematopoietic stem cell function ( e.g. Lyl1 ( 61 ) , Stat3 ( 62 ) ) , and transcription factors with more lineage restricted functions ( e.g. Ebf1 ( 63 ) , Gata1 ( 64 ) , Nfe2 ( 65 ) ) . Our findings indicate that already at the HB stage , LMO2 primes transcription factor genes which will be upregulated at later stages of haematopoiesis and thus regulates all steps of haematopoietic development .