Análise das regiões promotoras dos genes de receptores olfatórios e de receptores de feromônios do tipo 1 / Analysis of promoter regions of the olfactory and type 1 vomeronasal receptor genes

AUTOR(ES)
DATA DE PUBLICAÇÃO

2008

RESUMO

In the mouse genome there are approximately 1000 genes that encode olfactory receptors (ORs) and 150 genes that encode type 1 vomeronasal receptors (V1Rs) dispersed in various chromosomes. Each olfactory or vomeronasal neuron selects one single allele from one single receptor gene (OR or V1R) for expression while the rest of the repertoire remains silenced. The mechanisms underlying OR and V1R gene expression are still unknown. The similarities of the pattern of expression in both types of olfactory sensory neurons suggest that the regulation of OR and V1R gene expression may be under the control of a common mechanism. Until now, promoter regions of different OR and V1R genes had not been extensively analyzed. We carried out a comprehensive analysis in which the upstream regions of a large number of different OR and V1R genes were compared. First, using the RLM-RACE strategy, combined with degenerate PCR we generated hundreds of complete 5UTR cDNAs for a total of 198 OR genes and 39 V1R genes. Then, these cDNAs were aligned against the mouse genome sequence and the transcription start sites (TSSs) were precisely determined. Sequences upstream of the TSSs were retrieved and searched for common DNA motifs that may play a role as cis-acting elements involved in the general regulation of OR and V1R gene expression. The analysis revealed the presence of motifs that resemble O/E-like sites overrepresented in the OR and V1R promoter regions. These O/E-like motifs specifically interact with nuclear protein prepared from olfactory epithelium, but not from brain and liver. 8 We also identified a new motif that does not resemble any known transcription factor binding site. Besides, this new motif is present in 77% of the 39 V1R promoter regions and in 52% of the 198 OR promoter regions analyzed, preferentially concentrated near the TSSs. Interestingly, binding assays indicate that this new motif interacts with nuclear proteins prepared from the vomeronasal and the olfactory epithelia, but not from brain, liver and lung. Our results indicate that OR and V1R genes share common promoter elements that may be binding sites for specific olfactory transcription factors and may play a role in a common mechanism of olfactory and vomeronasal gene regulation

ASSUNTO(S)

vomeronasal receptor expressão gênica fator de transcrição receptor vomeronasal gene expression olfactory receptor feromônios olfato promoter transcription factor promotor receptor olfatório regulação gênica

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