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 Clim/Ldb/Nli. Although one family member, Clim-2/Ldb-1/Nli, is highly expressed in epidermal keratinocytes, no nuclear LIM domain factor is known to be expressed in epidermis. Therefore, we used the conserved LIM-interaction domain of Clim coregulators to screen for LIM domain factors in adult and embryonic mouse skin expression libraries and isolated a factor that is highly 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 with Clim-2 in epidermis and in several other regions, including epithelial cells of the gastrointestinal, respiratory and genitourinary tracts, developing cartilage, pituitary gland, and discrete regions of the central and peripheral nervous system. Like LMO-2, LMO-4 interacts strongly with Clim factors 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 the mouse homologue of Drosophila Deformed epidermal autoregulatory factor 1 (DEAF-1), a DNA-binding protein that interacts with regulatory sequences first described in the Deformed epidermal autoregulatory element. The interaction between LMO-4 and mouse DEAF-1 maps to a proline-rich C-terminal domain of mouse DEAF-1, distinct from the helix-loop-helix and GATA domains previously shown to interact with LMOs, thus defining an additional LIM-interacting domain.
Sugihara
T M
TM
Division of Endocrinology and Metabolism, Department and School of Medicine, University of California-San Diego, La Jolla, CA 92093, USA.
Bach
I
I
Kioussi
C
C
Rosenfeld
M G
MG
Andersen
B
B
D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D003001:Cloning, Molecular; D016384:Consensus Sequence; D017124:Conserved Sequence; D004268:DNA-Binding Proteins; D004330:Drosophila; D004622:Embryo, Mammalian; D004625:Embryo, Nonmammalian; D000078404:Epidermal Cells; D004817:Epidermis / Q000196:embryology / Q000378:metabolism; D005786:Gene Expression Regulation; D006197:Hair / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D018398:Homeodomain Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D060588:LIM Domain Proteins; D051379:Mice; D008969:Molecular Sequence Data; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D012867:Skin / Q000166:cytology / Q000196:embryology / Q000378:metabolism*; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; C486312:LDB1 protein, human; D060588:LIM Domain Proteins; C114905:LMO4 protein, human; C102084:Ldb1 protein, mouse; C491976:Lmo4 protein, mouse; D011994:Recombinant Proteins; D014157:Transcription Factors