Transcriptional regulation of pituitary POMC is conserved at the vertebrate extremes despite great promoter sequence divergence

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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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Autores principales:	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.
Formato:	Artículo publishedVersion
Publicado:	2007
Materias:	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
Acceso en línea:	http://hdl.handle.net/20.500.12110/paper_08888809_v21_n11_p2738_Bumaschny https://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=artiaex&d=paper_08888809_v21_n11_p2738_Bumaschny_oai
Aporte de:	Repositorio Digital de la Universidad de Buenos Aires (UBA) de Universidad de Buenos Aires

id	I28-R145-paper_08888809_v21_n11_p2738_Bumaschny_oai
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spelling	I28-R145-paper_08888809_v21_n11_p2738_Bumaschny_oai2024-08-16 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. 2007 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. application/pdf http://hdl.handle.net/20.500.12110/paper_08888809_v21_n11_p2738_Bumaschny info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar Mol. Endocrinol. 2007;21(11):2738-2749 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 Transcriptional regulation of pituitary POMC is conserved at the vertebrate extremes despite great promoter sequence divergence info:eu-repo/semantics/article info:ar-repo/semantics/artículo info:eu-repo/semantics/publishedVersion https://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=artiaex&d=paper_08888809_v21_n11_p2738_Bumaschny_oai
institution	Universidad de Buenos Aires
institution_str	I-28
repository_str	R-145
collection	Repositorio Digital de la Universidad de Buenos Aires (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	Artículo Artículo publishedVersion
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
publishDate	2007
url	http://hdl.handle.net/20.500.12110/paper_08888809_v21_n11_p2738_Bumaschny https://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=artiaex&d=paper_08888809_v21_n11_p2738_Bumaschny_oai
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Transcriptional regulation of pituitary POMC is conserved at the vertebrate extremes despite great promoter sequence divergence

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