Transcriptional regulation of pituitary POMC is conserved at the vertebrate extremes despite great promoter sequence divergence
| Autor: | Bumaschny, V.F., De Souza, F.S.J., Leal, R.A.L., Santangelo, A.M., Baetscher, M., Levi, D.H., Low, M.J., Rubinstein, M. |
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| Jazyk: | angličtina |
| Rok vydání: | 2007 |
| Předmět: |
proopiomelanocortin
Pro-Opiomelanocortin sequence analysis Transcription Genetic Amino Acid Motifs Teleostei Mice Cricetinae genetic variability Tetraodon genetic conservation Phylogeny teleost article Fishes adrenalectomy reporter gene female Tetraodon nigroviridis priority journal Pituitary Gland sequence alignment Mammalia cell nucleus receptor Promoter Regions (Genetics) transcription regulation proopiomelanocortin gene hormonal regulation gene locus animal experiment DNA sequence DNA flanking region Mice Transgenic gene sequence CHO Cells animal tissue promoter region Cricetulus Species Specificity Animals Mus musculus controlled study gene protein motif molecular phylogeny mouse Vertebrata nonhuman gene deletion corticotropin release transgenic mouse Gene Expression Regulation orthology |
| Zdroj: | Mol. Endocrinol. 2007;21(11):2738-2749 Biblioteca Digital (UBA-FCEN) Universidad Nacional de Buenos Aires. Facultad de Ciencias Exactas y Naturales instacron:UBA-FCEN |
| Popis: | The stress response involves complex physiological mechanisms that maximize behavioral efficacy during attack or defense and is highly conserved in all vertebrates. Key mediators of the stress response are pituitary hormones encoded by the proopiomelanocortin gene (POMC). Despite conservation of physiological function and expression pattern of POMC in all vertebrates, phylogenetic footprinting analyses at the POMC locus across vertebrates failed to detect conserved noncoding sequences with potential regulatory function. To investigate whether ortholog POMC promoters from extremely distant vertebrates are functionally conserved, we used 5′-flanking sequences of the teleost fish Tetraodon nigroviridis POMCα gene to produce transgenic mice. Tetraodon POMCα promoter targeted reporter gene expression exclusively to mouse pituitary cells that normally express Pomc. Importantly, transgenic expression in mouse corticotrophs was increased after adrenalectomy. To understand how conservation of precise gene expression mechanisms coexists with great sequence divergence, we investigated whether very short elements are still conserved in all vertebrate POMC promoters. Multiple local sequence alignments that consider phylogenetic relationships of ortholog regions identified a unique 10-bp motif GTGCTAA(T/G)CC that is usually present in two copies in POMC 5′-flanking sequences of all vertebrates. Underlined nucleotides represent totally conserved sequences. Deletion of these paired motifs from Tetraodon POMCα promoter markedly reduced its transcriptional activity in a mouse corticotropic cell line and in pituitary POMC cells of transgenic mice. In mammals, the conserved motifs correspond to reported binding sites for pituitary-specific nuclear proteins that participate in POMC transcriptional regulation. Together, these results demonstrate that mechanisms that participate in pituitary-specific and hormonally regulated expression of POMC have been preserved since mammals and teleosts diverged from a common ancestor 450 million years ago despite great promoter sequence divergence. Copyright © 2007 by The Endocrine Society. Fil:Santangelo, A.M. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Rubinstein, M. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. |
| Databáze: | OpenAIRE |
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