Enhancer turnover and conserved regulatory function in vertebrate evolution
Mutations in regulatory regions including enhancers are an important source of variation and innovation during evolution. Enhancers can evolve by changes in the sequence, arrangement and repertoire of transcription factor binding sites, but whole enhancers can also be lost or gained in certain linea...
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todo:paper_09628436_v368_n1632_p_Domene2023-10-03T15:54:14Z Enhancer turnover and conserved regulatory function in vertebrate evolution Domené, S. Bumaschny, V.F. de Souza, F.S.J. Franchini, L.F. Nasif, S. Low, M.J. Rubinstein, M. Comparative genomics Hypothalamus Mammals Proopiomelanocortin Teleosts Transgenic zebrafish cyprinid evolutionary biology gene expression hormone mammal mutation neurology turnover POMC protein, zebrafish proopiomelanocortin zebrafish protein animal article biology comparative genomics enhancer region gene expression regulation genetics hypothalamus immunohistochemistry in situ hybridization mammal metabolism molecular evolution mutation nerve cell nucleotide sequence teleost transgenic animal transgenic zebrafish vertebrate zebra fish comparative genomics hypothalamus mammals proopiomelanocortin teleosts transgenic zebrafish Animals Animals, Genetically Modified Computational Biology Conserved Sequence Enhancer Elements, Genetic Evolution, Molecular Gene Expression Regulation Immunohistochemistry In Situ Hybridization Mutation Neurons Pro-Opiomelanocortin Vertebrates Zebrafish Zebrafish Proteins Mutations in regulatory regions including enhancers are an important source of variation and innovation during evolution. Enhancers can evolve by changes in the sequence, arrangement and repertoire of transcription factor binding sites, but whole enhancers can also be lost or gained in certain lineages in a process of turnover. The proopiomelanocortin gene (Pomc), which encodes a prohormone, is expressed in the pituitary and hypothalamus of all jawed vertebrates. We have previously described that hypothalamic Pomc expression in mammals is controlled by two enhancers- nPE1 and nPE2-that are derived from transposable elements and that presumably replaced the ancestral neuronal Pomc regulatory regions. Here, we show that nPE1 and nPE2, even though they are mammalian novelties with no homologous counterpart in other vertebrates, nevertheless can drive gene expression specifically to POMC neurons in the hypothalamus of larval and adult transgenic zebrafish. This indicates that when neuronal Pomc enhancers originated de novo during early mammalian evolution, the newly created cis- and trans-codes were similar to the ancestral ones. We also identify the neuronal regulatory region of zebrafish pomca and confirm that it is not homologous to the mammalian enhancers. Our work sheds light on the process of gene regulatory evolution by showing how a locus can undergo enhancer turnover and nevertheless maintain the ancestral transcriptional output. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_09628436_v368_n1632_p_Domene |
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Universidad de Buenos Aires |
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I-28 |
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R-134 |
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Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
Comparative genomics Hypothalamus Mammals Proopiomelanocortin Teleosts Transgenic zebrafish cyprinid evolutionary biology gene expression hormone mammal mutation neurology turnover POMC protein, zebrafish proopiomelanocortin zebrafish protein animal article biology comparative genomics enhancer region gene expression regulation genetics hypothalamus immunohistochemistry in situ hybridization mammal metabolism molecular evolution mutation nerve cell nucleotide sequence teleost transgenic animal transgenic zebrafish vertebrate zebra fish comparative genomics hypothalamus mammals proopiomelanocortin teleosts transgenic zebrafish Animals Animals, Genetically Modified Computational Biology Conserved Sequence Enhancer Elements, Genetic Evolution, Molecular Gene Expression Regulation Immunohistochemistry In Situ Hybridization Mutation Neurons Pro-Opiomelanocortin Vertebrates Zebrafish Zebrafish Proteins |
| spellingShingle |
Comparative genomics Hypothalamus Mammals Proopiomelanocortin Teleosts Transgenic zebrafish cyprinid evolutionary biology gene expression hormone mammal mutation neurology turnover POMC protein, zebrafish proopiomelanocortin zebrafish protein animal article biology comparative genomics enhancer region gene expression regulation genetics hypothalamus immunohistochemistry in situ hybridization mammal metabolism molecular evolution mutation nerve cell nucleotide sequence teleost transgenic animal transgenic zebrafish vertebrate zebra fish comparative genomics hypothalamus mammals proopiomelanocortin teleosts transgenic zebrafish Animals Animals, Genetically Modified Computational Biology Conserved Sequence Enhancer Elements, Genetic Evolution, Molecular Gene Expression Regulation Immunohistochemistry In Situ Hybridization Mutation Neurons Pro-Opiomelanocortin Vertebrates Zebrafish Zebrafish Proteins Domené, S. Bumaschny, V.F. de Souza, F.S.J. Franchini, L.F. Nasif, S. Low, M.J. Rubinstein, M. Enhancer turnover and conserved regulatory function in vertebrate evolution |
| topic_facet |
Comparative genomics Hypothalamus Mammals Proopiomelanocortin Teleosts Transgenic zebrafish cyprinid evolutionary biology gene expression hormone mammal mutation neurology turnover POMC protein, zebrafish proopiomelanocortin zebrafish protein animal article biology comparative genomics enhancer region gene expression regulation genetics hypothalamus immunohistochemistry in situ hybridization mammal metabolism molecular evolution mutation nerve cell nucleotide sequence teleost transgenic animal transgenic zebrafish vertebrate zebra fish comparative genomics hypothalamus mammals proopiomelanocortin teleosts transgenic zebrafish Animals Animals, Genetically Modified Computational Biology Conserved Sequence Enhancer Elements, Genetic Evolution, Molecular Gene Expression Regulation Immunohistochemistry In Situ Hybridization Mutation Neurons Pro-Opiomelanocortin Vertebrates Zebrafish Zebrafish Proteins |
| description |
Mutations in regulatory regions including enhancers are an important source of variation and innovation during evolution. Enhancers can evolve by changes in the sequence, arrangement and repertoire of transcription factor binding sites, but whole enhancers can also be lost or gained in certain lineages in a process of turnover. The proopiomelanocortin gene (Pomc), which encodes a prohormone, is expressed in the pituitary and hypothalamus of all jawed vertebrates. We have previously described that hypothalamic Pomc expression in mammals is controlled by two enhancers- nPE1 and nPE2-that are derived from transposable elements and that presumably replaced the ancestral neuronal Pomc regulatory regions. Here, we show that nPE1 and nPE2, even though they are mammalian novelties with no homologous counterpart in other vertebrates, nevertheless can drive gene expression specifically to POMC neurons in the hypothalamus of larval and adult transgenic zebrafish. This indicates that when neuronal Pomc enhancers originated de novo during early mammalian evolution, the newly created cis- and trans-codes were similar to the ancestral ones. We also identify the neuronal regulatory region of zebrafish pomca and confirm that it is not homologous to the mammalian enhancers. Our work sheds light on the process of gene regulatory evolution by showing how a locus can undergo enhancer turnover and nevertheless maintain the ancestral transcriptional output. |
| format |
JOUR |
| author |
Domené, S. Bumaschny, V.F. de Souza, F.S.J. Franchini, L.F. Nasif, S. Low, M.J. Rubinstein, M. |
| author_facet |
Domené, S. Bumaschny, V.F. de Souza, F.S.J. Franchini, L.F. Nasif, S. Low, M.J. Rubinstein, M. |
| author_sort |
Domené, S. |
| title |
Enhancer turnover and conserved regulatory function in vertebrate evolution |
| title_short |
Enhancer turnover and conserved regulatory function in vertebrate evolution |
| title_full |
Enhancer turnover and conserved regulatory function in vertebrate evolution |
| title_fullStr |
Enhancer turnover and conserved regulatory function in vertebrate evolution |
| title_full_unstemmed |
Enhancer turnover and conserved regulatory function in vertebrate evolution |
| title_sort |
enhancer turnover and conserved regulatory function in vertebrate evolution |
| url |
http://hdl.handle.net/20.500.12110/paper_09628436_v368_n1632_p_Domene |
| work_keys_str_mv |
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1807324423792885760 |