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

Autores
Bumaschny, Viviana Florencia; Silva Junqueira de Souza, Flavio; López Leal, Rodrigo A.; Santangelo, Andrea Mariana; Baetscher, Manfred; Levi, Diego H.; Low, Malcolm J.; Rubinstein, Marcelo
Año de publicación
2007
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
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.
Fil: Bumaschny, Viviana Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Silva Junqueira de Souza, Flavio. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: López Leal, Rodrigo A.. Centro de Estudios Cientificos; Chile
Fil: Santangelo, Andrea Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Baetscher, Manfred. Harvard University; Estados Unidos
Fil: Levi, Diego H.. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Low, Malcolm J.. Oregon Health and Science University; Estados Unidos
Fil: Rubinstein, Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Fisiología, Biología Molecular y Celular; Argentina. Centro de Estudios Cientificos; Chile. Oregon Health and Science University; Estados Unidos
Materia
Pomc
Tetraodon
Evolution
Pituitary
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/79815
Acceder
id CONICETDig_28fbaff10c2c80b37e6fc42ec2d1079e
oai_identifier_str oai:ri.conicet.gov.ar:11336/79815
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Transcriptional regulation of pituitary POMC is conserved at the vertebrate extremes despite great promoter sequence divergenceBumaschny, Viviana FlorenciaSilva Junqueira de Souza, FlavioLópez Leal, Rodrigo A.Santangelo, Andrea MarianaBaetscher, ManfredLevi, Diego H.Low, Malcolm J.Rubinstein, MarceloPomcTetraodonEvolutionPituitaryhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1The 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.Fil: Bumaschny, Viviana Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Silva Junqueira de Souza, Flavio. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: López Leal, Rodrigo A.. Centro de Estudios Cientificos; ChileFil: Santangelo, Andrea Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Baetscher, Manfred. Harvard University; Estados UnidosFil: Levi, Diego H.. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Low, Malcolm J.. Oregon Health and Science University; Estados UnidosFil: Rubinstein, Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Fisiología, Biología Molecular y Celular; Argentina. Centro de Estudios Cientificos; Chile. Oregon Health and Science University; Estados UnidosEndocrine Society2007-11info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/79815Bumaschny, Viviana Florencia; Silva Junqueira de Souza, Flavio; López Leal, Rodrigo A.; Santangelo, Andrea Mariana; Baetscher, Manfred; et al.; Transcriptional regulation of pituitary POMC is conserved at the vertebrate extremes despite great promoter sequence divergence; Endocrine Society; Molecular Endocrinology; 21; 11; 11-2007; 2738-27490888-8809CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pubmed/17698954info:eu-repo/semantics/altIdentifier/doi/10.1210/me.2006-0557info:eu-repo/semantics/altIdentifier/url/https://academic.oup.com/mend/article/21/11/2738/2738430info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:54:39Zoai:ri.conicet.gov.ar:11336/79815instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 09:54:40.042CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Transcriptional regulation of pituitary POMC is conserved at the vertebrate extremes despite great promoter sequence divergence
title Transcriptional regulation of pituitary POMC is conserved at the vertebrate extremes despite great promoter sequence divergence
spellingShingle Transcriptional regulation of pituitary POMC is conserved at the vertebrate extremes despite great promoter sequence divergence
Bumaschny, Viviana Florencia
Pomc
Tetraodon
Evolution
Pituitary
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
dc.creator.none.fl_str_mv Bumaschny, Viviana Florencia
Silva Junqueira de Souza, Flavio
López Leal, Rodrigo A.
Santangelo, Andrea Mariana
Baetscher, Manfred
Levi, Diego H.
Low, Malcolm J.
Rubinstein, Marcelo
author Bumaschny, Viviana Florencia
author_facet Bumaschny, Viviana Florencia
Silva Junqueira de Souza, Flavio
López Leal, Rodrigo A.
Santangelo, Andrea Mariana
Baetscher, Manfred
Levi, Diego H.
Low, Malcolm J.
Rubinstein, Marcelo
author_role author
author2 Silva Junqueira de Souza, Flavio
López Leal, Rodrigo A.
Santangelo, Andrea Mariana
Baetscher, Manfred
Levi, Diego H.
Low, Malcolm J.
Rubinstein, Marcelo
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Pomc
Tetraodon
Evolution
Pituitary
topic Pomc
Tetraodon
Evolution
Pituitary
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv 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.
Fil: Bumaschny, Viviana Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Silva Junqueira de Souza, Flavio. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: López Leal, Rodrigo A.. Centro de Estudios Cientificos; Chile
Fil: Santangelo, Andrea Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Baetscher, Manfred. Harvard University; Estados Unidos
Fil: Levi, Diego H.. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Low, Malcolm J.. Oregon Health and Science University; Estados Unidos
Fil: Rubinstein, Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Fisiología, Biología Molecular y Celular; Argentina. Centro de Estudios Cientificos; Chile. Oregon Health and Science University; Estados Unidos
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.
publishDate 2007
dc.date.none.fl_str_mv 2007-11
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/79815
Bumaschny, Viviana Florencia; Silva Junqueira de Souza, Flavio; López Leal, Rodrigo A.; Santangelo, Andrea Mariana; Baetscher, Manfred; et al.; Transcriptional regulation of pituitary POMC is conserved at the vertebrate extremes despite great promoter sequence divergence; Endocrine Society; Molecular Endocrinology; 21; 11; 11-2007; 2738-2749
0888-8809
CONICET Digital
CONICET
url http://hdl.handle.net/11336/79815
identifier_str_mv Bumaschny, Viviana Florencia; Silva Junqueira de Souza, Flavio; López Leal, Rodrigo A.; Santangelo, Andrea Mariana; Baetscher, Manfred; et al.; Transcriptional regulation of pituitary POMC is conserved at the vertebrate extremes despite great promoter sequence divergence; Endocrine Society; Molecular Endocrinology; 21; 11; 11-2007; 2738-2749
0888-8809
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pubmed/17698954
info:eu-repo/semantics/altIdentifier/doi/10.1210/me.2006-0557
info:eu-repo/semantics/altIdentifier/url/https://academic.oup.com/mend/article/21/11/2738/2738430
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Endocrine Society
publisher.none.fl_str_mv Endocrine Society
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.13397

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