A family of LIM domain-associated cofactors confer transcriptional synergism between LIM and Otx homeodomain proteins.
The essential roles of LIM homeodomain proteins in cell fate determination during development have been demonstrated in organisms as divergent as Drosophila and higher mammals. We have isolated murine cDNAs encoding two highly homologous proteins that specifically interact with the LIM domains of P-Lim/Lhx3 and several other LIM homeodomain factors. Transcripts encoding these factors can be detected as early as mouse E8.5, with maximal expression observed in regions of the embryo in which the LIM homeodomain factors P-Lim/Lhx3, Isl-1, and LH-2 are selectively expressed. These proteins can potentiate transactivation by P-Lim/Lhx-3 and are required for a synergistic activation of the glycoprotein hormone alpha-subunit promoter by P-Lim/Lhx3 and a pituitary Otx class homeodomain transcription factor, with which they also specifically associate. Our results link LIM homeodomain proteins and members of the Otx class of transcription factors in gene activation events during embryogenesis via the actions of specific cofactors.
Bach
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I
Howard Hughes Medical Institute, Eukaryotic Regulatory Biology Program, University of California, San Diego, School of Medicine, La Jolla 92093-0648, USA. ibach@ucsd.edu
Carrière
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C
Ostendorff
H P
HP
Andersen
B
B
Rosenfeld
M G
MG
D000595:Amino Acid Sequence; D000818:Animals; D003001:Cloning, Molecular; D004268:DNA-Binding Proteins; D004622:Embryo, Mammalian / Q000378:metabolism; D018398:Homeodomain Proteins / Q000378:metabolism*; D017403:In Situ Hybridization; D060588:LIM Domain Proteins; D060850:LIM-Homeodomain Proteins; D051379:Mice; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins; D051761:Paired Box Transcription Factors; D011485:Protein Binding; D011994:Recombinant Proteins / Q000378:metabolism; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D015533:Transcriptional Activation
D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D060588:LIM Domain Proteins; D060850:LIM-Homeodomain Proteins; C102084:Ldb1 protein, mouse; C106649:Ldb2 protein, mouse; C094898:Lhx3 protein; D009419:Nerve Tissue Proteins; D051761:Paired Box Transcription Factors; D011994:Recombinant Proteins; D014157:Transcription Factors; C101485:homeobox protein PITX1; C063843:insulin gene enhancer binding protein Isl-1