LIM-homeodomain (LIM-HD) transcription factors act as key developmental regulators, both through their ability to bind DNA through homeodomain:DNA interactions, and through their ability to form larger complexes through protein:protein interactions. The LIM-HD protein Islet-1 (Isl1) has been shown to be involved in the development of many tissues. However, many of the mechanisms behind its action have yet to be determined.
Isl1 contains a homeodomain that allows it to bind directly to DNA. However, given the low DNA-binding specificity of this homeodomain, it primarily acts to influence gene expression through the formation of transcriptional complexes. The protein:protein interactions involved in the formation of these complexes commonly occur through two regions of the protein: two tandem LIM domains at the N-terminus, and a LIM interaction domain (LID) at the C-terminus.
The action of these protein interaction domains is well illustrated in the Ldb1/Isl1/Lhx3 complex, which is formed during motor neuron development. Isl1LIM forms an interaction with Ldb1LID, while Isl1LID interacts with Lhx3LIM. This complex then activates the expression of motor neuron genes.
In order to identify other such transcriptional complexes relevant to development, yeast two-hybrid mating screens have been used, utilising Isl1 as bait. This has so far resulted in a pool of approximately 100 potential Isl1-interacting proteins. Once fully validated, these interactions may provide understanding into the mechanism of action of Isl1 in distinct tissues, giving more insight into how Isl1 plays such a diverse role in development.