Transcriptional regulation of pituitary POMC is conserved at the vertebrate extremes despite great promoter sequence divergence
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 phy...
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todo:paper_08888809_v21_n11_p2738_Bumaschny2023-10-03T15:41:09Z Transcriptional regulation of pituitary POMC is conserved at the vertebrate extremes despite great promoter sequence divergence 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. cell nucleus receptor proopiomelanocortin adrenalectomy animal experiment animal tissue article controlled study corticotropin release DNA flanking region DNA sequence female gene gene deletion gene locus gene sequence genetic conservation genetic variability hormonal regulation molecular phylogeny mouse nonhuman orthology priority journal promoter region proopiomelanocortin gene protein motif reporter gene sequence alignment sequence analysis teleost transcription regulation transgenic mouse Amino Acid Motifs Animals CHO Cells Cricetinae Cricetulus Fishes Gene Expression Regulation Mice Mice, Transgenic Phylogeny Pituitary Gland Pro-Opiomelanocortin Promoter Regions (Genetics) Species Specificity Transcription, Genetic Mammalia Mus musculus Teleostei Tetraodon Tetraodon nigroviridis Vertebrata 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. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_08888809_v21_n11_p2738_Bumaschny |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
cell nucleus receptor proopiomelanocortin adrenalectomy animal experiment animal tissue article controlled study corticotropin release DNA flanking region DNA sequence female gene gene deletion gene locus gene sequence genetic conservation genetic variability hormonal regulation molecular phylogeny mouse nonhuman orthology priority journal promoter region proopiomelanocortin gene protein motif reporter gene sequence alignment sequence analysis teleost transcription regulation transgenic mouse Amino Acid Motifs Animals CHO Cells Cricetinae Cricetulus Fishes Gene Expression Regulation Mice Mice, Transgenic Phylogeny Pituitary Gland Pro-Opiomelanocortin Promoter Regions (Genetics) Species Specificity Transcription, Genetic Mammalia Mus musculus Teleostei Tetraodon Tetraodon nigroviridis Vertebrata |
| spellingShingle |
cell nucleus receptor proopiomelanocortin adrenalectomy animal experiment animal tissue article controlled study corticotropin release DNA flanking region DNA sequence female gene gene deletion gene locus gene sequence genetic conservation genetic variability hormonal regulation molecular phylogeny mouse nonhuman orthology priority journal promoter region proopiomelanocortin gene protein motif reporter gene sequence alignment sequence analysis teleost transcription regulation transgenic mouse Amino Acid Motifs Animals CHO Cells Cricetinae Cricetulus Fishes Gene Expression Regulation Mice Mice, Transgenic Phylogeny Pituitary Gland Pro-Opiomelanocortin Promoter Regions (Genetics) Species Specificity Transcription, Genetic Mammalia Mus musculus Teleostei Tetraodon Tetraodon nigroviridis Vertebrata 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. Transcriptional regulation of pituitary POMC is conserved at the vertebrate extremes despite great promoter sequence divergence |
| topic_facet |
cell nucleus receptor proopiomelanocortin adrenalectomy animal experiment animal tissue article controlled study corticotropin release DNA flanking region DNA sequence female gene gene deletion gene locus gene sequence genetic conservation genetic variability hormonal regulation molecular phylogeny mouse nonhuman orthology priority journal promoter region proopiomelanocortin gene protein motif reporter gene sequence alignment sequence analysis teleost transcription regulation transgenic mouse Amino Acid Motifs Animals CHO Cells Cricetinae Cricetulus Fishes Gene Expression Regulation Mice Mice, Transgenic Phylogeny Pituitary Gland Pro-Opiomelanocortin Promoter Regions (Genetics) Species Specificity Transcription, Genetic Mammalia Mus musculus Teleostei Tetraodon Tetraodon nigroviridis Vertebrata |
| description |
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. |
| format |
JOUR |
| author |
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. |
| author_facet |
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. |
| author_sort |
Bumaschny, V.F. |
| title |
Transcriptional regulation of pituitary POMC is conserved at the vertebrate extremes despite great promoter sequence divergence |
| title_short |
Transcriptional regulation of pituitary POMC is conserved at the vertebrate extremes despite great promoter sequence divergence |
| title_full |
Transcriptional regulation of pituitary POMC is conserved at the vertebrate extremes despite great promoter sequence divergence |
| title_fullStr |
Transcriptional regulation of pituitary POMC is conserved at the vertebrate extremes despite great promoter sequence divergence |
| title_full_unstemmed |
Transcriptional regulation of pituitary POMC is conserved at the vertebrate extremes despite great promoter sequence divergence |
| title_sort |
transcriptional regulation of pituitary pomc is conserved at the vertebrate extremes despite great promoter sequence divergence |
| url |
http://hdl.handle.net/20.500.12110/paper_08888809_v21_n11_p2738_Bumaschny |
| work_keys_str_mv |
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1807322766689435648 |