Mouse Deformed epidermal autoregulatory factor 1 recruits a LIM domain factor, LMO-4, and CLIM coregulators

Nuclear LIM domains interact with a family of coregulators referred to as C lim/Ldb/Nli. Although one family member, Clim-2/Ldb-1/Nli, is highly expres sed in epidermal keratinocytes, no nuclear LIM domain factor is known to be expressed in epidermis, Therefore, we used the conserved LIM-interaction d omain of Clim coregulators to screen for LIM domain factors in adult and em bryonic mouse skin expression libraries and isolated a factor that is highl y homologous to the previously described LIM-only proteins LMO-1, -2, and - 3, This factor, referred to as LMO-4, is expressed in overlapping manner wi th Clim-2 in epidermis and in several other regions, including epithelial c ells of the gastrointestinal, respiratory and genitourinary tracts, develop ing cartilage, pituitary gland, and discrete regions of the central and per ipheral nervous system. Like LMO-2, LMO-4 interacts strongly with Clim fact ors via its LIM domain. Because LMO/Clim complexes are thought to regulate gene expression by associating with DNA-binding proteins, we used LMO-4 as a bait to screen for such DNA-binding proteins in epidermis and isolated th e mouse homologue of Drosophila Deformed epidermal autoregulatory factor 1 (DEAF-I), a DNA-binding protein that interacts with regulatory sequences fi rst described in the Deformed epidermal autoregulatory element. The interac tion between LMO-4 and mouse DEAF-1 maps to a proline-rich C-terminal domai n of mouse DEAF-1, distinct from the helix-loop-helix and GATA domains prev iously shown to interact with LMOs, thus defining an additional LIM-interac ting domain.