THE NUCLEAR LIM DOMAIN INTERACTOR NLI MEDIATES HOMODIMERIZATION AND HETERODIMERIZATION OF LIM DOMAIN TRANSCRIPTION FACTORS

LIM domain-containing transcription factors are required for embryonic survival and for the determination of many cell types. The combinator ial expression of the LIM homeodomain proteins Isl1, Isl2, Lhx1, and L hx3 in subsets of developing motor neurons correlates with the future organization of these neurons into motor columns with distinct innerva tion targets, implying a functional role for LIM homeodomain protein c ombinations in the specification of neuronal identity, NLI is a widely expressed, dimeric protein that has been shown to specifically intera ct with the LIM domains of LIM domain-containing transcription factors , The present studies demonstrate that NLI mediates home-and heteromer ic complex formation between LIM domain transcription factors, requiri ng both the N-terminal dimerization and C-terminal LIM interaction dom ains of NLI, Although the interaction between most LIM homeodomain pro teins is dependent on NLI, a direct interaction between the LIM domain s of Lhx3 and the homeodomains of Isl1 and Isl2 was also observed. Thi s interaction was disrupted by NLI, demonstrating that the conformatio nal state of Lhx3-Isl1/Isl2 complexes is modified by NLI, Evidence ind icating that NLI facilitates long range enhancer-promoter interactions suggests that NLI-dependent LIM domain transcription factor complexes are involved in communication between transcriptional control element s.