Changing homeodomain residues 2 and 3 of Hoxa1 alters its activity in a cell-type and enhancer dependent manner
| Autor: | Sophie Remacle, Chloë Shaw-Jackson, Christelle Matis, Xavier Lampe, René Rezsohazy, Jacques J. Picard |
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| Přispěvatelé: | UCL - MD/MIGE - Département de microbiologie, d'immunologie et de génétique |
| Rok vydání: | 2002 |
| Předmět: |
Transcriptional Activation
Arginine Recombinant Fusion Proteins Lysine Mutant Biology Article Cell Line Structure-Activity Relationship Protein structure Proto-Oncogene Proteins Genetics Animals Humans Enhancer Elements (Genetics) Asparagine Enhancer Transcription factor Alanine Homeodomain Proteins Pre-B-Cell Leukemia Transcription Factor 1 Herpes Simplex Virus Protein Vmw65 Trans-Activation (Genetics) Protein Structure Tertiary DNA-Binding Proteins Enhancer Elements Genetic Biochemistry Amino Acid Substitution embryonic structures Trans-Activators Somatostatin Transcription Factors |
| Zdroj: | Nucleic Acids Research, Vol. 30, no. 12, p. 2663-2668 (2002) |
| ISSN: | 1362-4962 |
| Popis: | The second and third amino acid residues of the N-terminal arm of most Hox protein homeodomains are basic (lysine or arginine), whereas they are asparagine and alanine, respectively, in the Hoxa1 homeodomain. Previous reports pinpointed these residues as specificity determinants in the function of Hoxa1 when it is acting as a monomer. However, in vitro data supported that these residues do not influence the target specificity of Hoxa1 in Pbx1a-Hoxa1 heterodimers. Here, we have analysed the transcriptional activity of a Hoxa1(NA-KR) mutant for which the asparagine and alanine residues of the homeodomain have been replaced by lysine and arginine, respectively. Comparison between the wild-type and mutant Hoxa1 reveals that they show distinct activity on the TSEII enhancer of the somatostatin gene, but that they are equally active in the presence of Pbx and Prep cofactors. This therefore corroborates the biochemical evidence having shown that the second and third residues of the homeodomain do not contribute to the DNA binding of Hoxa1-Pbx dimers. However, on the hoxb1 autoregulatory enhancer, Hoxa1 and Hoxa1(NA-KR) may display distinct activity despite the presence of Pbx, in a cell-type dependent manner. Therefore, our data suggest that, depending on the enhancer, these residues may contribute to the functional specificity of Hoxa1 and that this contribution may not be abrogated by the interaction with Pbx. |
| Databáze: | OpenAIRE |
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