5meCpG Epigenetic Marks Neighboring a Primate-Conserved Core Promoter Short Tandem Repeat Indicate X-Chromosome Inactivation

Autores
Brum Machado, Filipe; Brum Machado, Fabricio; Faria, Milena Amendro; Lovate, Viviane Lamim; Alves da Silva, Antonio Francisco; Radic, Claudia Pamela; De Bras, Carlos Daniel; Lopes Rios, Alvaro Fabricio; de Sousa Lopes, Susana Marina Chuva; da Silveira, Leonardo Serafim; Ruiz Miranda, Carlos Ramon; Silveira Ramos, Ester; Medina-Acosta, Enrique
Año de publicación
2014
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
X-chromosome inactivation (XCI) is the epigenetic transcriptional silencing of an X-chromosome during the early stages of embryonic development in female eutherian mammals. XCI assures monoallelic expression in each cell and compensation for dosage-sensitive X-linked genes between females (XX) and males (XY). DNA methylation at the carbon-5 position of the cytosine pyrimidine ring in the context of a CpG dinucleotide sequence (5meCpG) in promoter regions is a key epigeneticmarker for transcriptional gene silencing. Using computational analysis, we revealed an extragenic tandem GAAA repeat 230-bp from the landmark CpG island of the human X-linked retinitis pigmentosa 2 RP2 promoter whose 5meCpG status correlates with XCI. We used this RP2 onshore tandem GAAA repeat to develop an allele-specific 5meCpG-based PCR assay that is highly concordant with the human androgen receptor (AR) exonic tandem CAG repeat-based standard HUMARA assay in discriminating active (Xa) from inactive (Xi) X-chromosomes. The RP2 onshore tandem GAAA repeat contains neutral features that are lacking in the AR disease-linked tandem CAG repeat, is highly polymorphic (heterozygosity rates approximately 0.8) and shows minimal variation in the Xa/Xi ratio. The combined informativeness of RP2/AR is approximately 0.97, and this assay excels at determining the 5meCpG status of alleles at the Xp (RP2) and Xq (AR) chromosome arms in a single reaction. These findings are relevant and directly translatable to nonhuman primate models of XCI in which the AR CAG-repeat is monomorphic. We conducted the RP2 onshore tandem GAAA repeat assay in the naturally occurring chimeric New World monkey marmoset (Callitrichidae) and found it to be informative. The RP2 onshore tandem GAAA repeat will facilitate studies on the variable phenotypic expression of dominant and recessive X-linked diseases, epigenetic changes in twins, the physiology of aging hematopoiesis, the pathogenesis of age-related hematopoietic malignancies and the clonality of cancers in human and nonhuman primates.
Fil: Brum Machado, Filipe. Universidade de Sao Paulo; Brasil
Fil: Brum Machado, Fabricio. Universidade Estadual Do Norte Fluminense Darcy Ribeiro; Brasil
Fil: Faria, Milena Amendro. Universidade Estadual Do Norte Fluminense Darcy Ribeiro; Brasil
Fil: Lovate, Viviane Lamim. Universidade Estadual Do Norte Fluminense Darcy Ribeiro; Brasil
Fil: Alves da Silva, Antonio Francisco. Universidade Estadual Do Norte Fluminense Darcy Ribeiro; Brasil
Fil: Radic, Claudia Pamela. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: De Bras, Carlos Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Lopes Rios, Alvaro Fabricio. Universidade Estadual Do Norte Fluminense Darcy Ribeiro; Brasil
Fil: de Sousa Lopes, Susana Marina Chuva. Leiden University; Países Bajos
Fil: da Silveira, Leonardo Serafim. Universidade Estadual Do Norte Fluminense Darcy Ribeiro; Brasil
Fil: Ruiz Miranda, Carlos Ramon. Universidade Estadual Do Norte Fluminense Darcy Ribeiro; Brasil
Fil: Silveira Ramos, Ester. Universidade de Sao Paulo; Brasil
Fil: Medina-Acosta, Enrique. Universidade Estadual Do Norte Fluminense Darcy Ribeiro; Brasil
Materia
Epigenetics
X-chromosome inactivation
HUMARA
RP2
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:11336/29456
Acceder
id CONICETDig_77e4de62b68dce97911eb9cf0d02db6b
oai_identifier_str oai:ri.conicet.gov.ar:11336/29456
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling 5meCpG Epigenetic Marks Neighboring a Primate-Conserved Core Promoter Short Tandem Repeat Indicate X-Chromosome InactivationBrum Machado, FilipeBrum Machado, FabricioFaria, Milena AmendroLovate, Viviane LamimAlves da Silva, Antonio FranciscoRadic, Claudia PamelaDe Bras, Carlos DanielLopes Rios, Alvaro Fabriciode Sousa Lopes, Susana Marina Chuvada Silveira, Leonardo SerafimRuiz Miranda, Carlos RamonSilveira Ramos, EsterMedina-Acosta, EnriqueEpigeneticsX-chromosome inactivationHUMARARP2https://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1X-chromosome inactivation (XCI) is the epigenetic transcriptional silencing of an X-chromosome during the early stages of embryonic development in female eutherian mammals. XCI assures monoallelic expression in each cell and compensation for dosage-sensitive X-linked genes between females (XX) and males (XY). DNA methylation at the carbon-5 position of the cytosine pyrimidine ring in the context of a CpG dinucleotide sequence (5meCpG) in promoter regions is a key epigeneticmarker for transcriptional gene silencing. Using computational analysis, we revealed an extragenic tandem GAAA repeat 230-bp from the landmark CpG island of the human X-linked retinitis pigmentosa 2 RP2 promoter whose 5meCpG status correlates with XCI. We used this RP2 onshore tandem GAAA repeat to develop an allele-specific 5meCpG-based PCR assay that is highly concordant with the human androgen receptor (AR) exonic tandem CAG repeat-based standard HUMARA assay in discriminating active (Xa) from inactive (Xi) X-chromosomes. The RP2 onshore tandem GAAA repeat contains neutral features that are lacking in the AR disease-linked tandem CAG repeat, is highly polymorphic (heterozygosity rates approximately 0.8) and shows minimal variation in the Xa/Xi ratio. The combined informativeness of RP2/AR is approximately 0.97, and this assay excels at determining the 5meCpG status of alleles at the Xp (RP2) and Xq (AR) chromosome arms in a single reaction. These findings are relevant and directly translatable to nonhuman primate models of XCI in which the AR CAG-repeat is monomorphic. We conducted the RP2 onshore tandem GAAA repeat assay in the naturally occurring chimeric New World monkey marmoset (Callitrichidae) and found it to be informative. The RP2 onshore tandem GAAA repeat will facilitate studies on the variable phenotypic expression of dominant and recessive X-linked diseases, epigenetic changes in twins, the physiology of aging hematopoiesis, the pathogenesis of age-related hematopoietic malignancies and the clonality of cancers in human and nonhuman primates.Fil: Brum Machado, Filipe. Universidade de Sao Paulo; BrasilFil: Brum Machado, Fabricio. Universidade Estadual Do Norte Fluminense Darcy Ribeiro; BrasilFil: Faria, Milena Amendro. Universidade Estadual Do Norte Fluminense Darcy Ribeiro; BrasilFil: Lovate, Viviane Lamim. Universidade Estadual Do Norte Fluminense Darcy Ribeiro; BrasilFil: Alves da Silva, Antonio Francisco. Universidade Estadual Do Norte Fluminense Darcy Ribeiro; BrasilFil: Radic, Claudia Pamela. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: De Bras, Carlos Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Lopes Rios, Alvaro Fabricio. Universidade Estadual Do Norte Fluminense Darcy Ribeiro; BrasilFil: de Sousa Lopes, Susana Marina Chuva. Leiden University; Países BajosFil: da Silveira, Leonardo Serafim. Universidade Estadual Do Norte Fluminense Darcy Ribeiro; BrasilFil: Ruiz Miranda, Carlos Ramon. Universidade Estadual Do Norte Fluminense Darcy Ribeiro; BrasilFil: Silveira Ramos, Ester. Universidade de Sao Paulo; BrasilFil: Medina-Acosta, Enrique. Universidade Estadual Do Norte Fluminense Darcy Ribeiro; BrasilPublic Library of Science2014-07info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/29456Brum Machado, Filipe; Brum Machado, Fabricio; Faria, Milena Amendro; Lovate, Viviane Lamim; Alves da Silva, Antonio Francisco; et al.; 5meCpG Epigenetic Marks Neighboring a Primate-Conserved Core Promoter Short Tandem Repeat Indicate X-Chromosome Inactivation; Public Library of Science; Plos One; 9; 7-2014; 1-131932-6203CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1371/journal.pone.0103714info:eu-repo/semantics/altIdentifier/url/http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0103714info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:44:42Zoai:ri.conicet.gov.ar:11336/29456instacron: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:34982025-09-29 09:44:42.607CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv 5meCpG Epigenetic Marks Neighboring a Primate-Conserved Core Promoter Short Tandem Repeat Indicate X-Chromosome Inactivation
title 5meCpG Epigenetic Marks Neighboring a Primate-Conserved Core Promoter Short Tandem Repeat Indicate X-Chromosome Inactivation
spellingShingle 5meCpG Epigenetic Marks Neighboring a Primate-Conserved Core Promoter Short Tandem Repeat Indicate X-Chromosome Inactivation
Brum Machado, Filipe
Epigenetics
X-chromosome inactivation
HUMARA
RP2
title_short 5meCpG Epigenetic Marks Neighboring a Primate-Conserved Core Promoter Short Tandem Repeat Indicate X-Chromosome Inactivation
title_full 5meCpG Epigenetic Marks Neighboring a Primate-Conserved Core Promoter Short Tandem Repeat Indicate X-Chromosome Inactivation
title_fullStr 5meCpG Epigenetic Marks Neighboring a Primate-Conserved Core Promoter Short Tandem Repeat Indicate X-Chromosome Inactivation
title_full_unstemmed 5meCpG Epigenetic Marks Neighboring a Primate-Conserved Core Promoter Short Tandem Repeat Indicate X-Chromosome Inactivation
title_sort 5meCpG Epigenetic Marks Neighboring a Primate-Conserved Core Promoter Short Tandem Repeat Indicate X-Chromosome Inactivation
dc.creator.none.fl_str_mv Brum Machado, Filipe
Brum Machado, Fabricio
Faria, Milena Amendro
Lovate, Viviane Lamim
Alves da Silva, Antonio Francisco
Radic, Claudia Pamela
De Bras, Carlos Daniel
Lopes Rios, Alvaro Fabricio
de Sousa Lopes, Susana Marina Chuva
da Silveira, Leonardo Serafim
Ruiz Miranda, Carlos Ramon
Silveira Ramos, Ester
Medina-Acosta, Enrique
author Brum Machado, Filipe
author_facet Brum Machado, Filipe
Brum Machado, Fabricio
Faria, Milena Amendro
Lovate, Viviane Lamim
Alves da Silva, Antonio Francisco
Radic, Claudia Pamela
De Bras, Carlos Daniel
Lopes Rios, Alvaro Fabricio
de Sousa Lopes, Susana Marina Chuva
da Silveira, Leonardo Serafim
Ruiz Miranda, Carlos Ramon
Silveira Ramos, Ester
Medina-Acosta, Enrique
author_role author
author2 Brum Machado, Fabricio
Faria, Milena Amendro
Lovate, Viviane Lamim
Alves da Silva, Antonio Francisco
Radic, Claudia Pamela
De Bras, Carlos Daniel
Lopes Rios, Alvaro Fabricio
de Sousa Lopes, Susana Marina Chuva
da Silveira, Leonardo Serafim
Ruiz Miranda, Carlos Ramon
Silveira Ramos, Ester
Medina-Acosta, Enrique
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Epigenetics
X-chromosome inactivation
HUMARA
RP2
topic Epigenetics
X-chromosome inactivation
HUMARA
RP2
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv X-chromosome inactivation (XCI) is the epigenetic transcriptional silencing of an X-chromosome during the early stages of embryonic development in female eutherian mammals. XCI assures monoallelic expression in each cell and compensation for dosage-sensitive X-linked genes between females (XX) and males (XY). DNA methylation at the carbon-5 position of the cytosine pyrimidine ring in the context of a CpG dinucleotide sequence (5meCpG) in promoter regions is a key epigeneticmarker for transcriptional gene silencing. Using computational analysis, we revealed an extragenic tandem GAAA repeat 230-bp from the landmark CpG island of the human X-linked retinitis pigmentosa 2 RP2 promoter whose 5meCpG status correlates with XCI. We used this RP2 onshore tandem GAAA repeat to develop an allele-specific 5meCpG-based PCR assay that is highly concordant with the human androgen receptor (AR) exonic tandem CAG repeat-based standard HUMARA assay in discriminating active (Xa) from inactive (Xi) X-chromosomes. The RP2 onshore tandem GAAA repeat contains neutral features that are lacking in the AR disease-linked tandem CAG repeat, is highly polymorphic (heterozygosity rates approximately 0.8) and shows minimal variation in the Xa/Xi ratio. The combined informativeness of RP2/AR is approximately 0.97, and this assay excels at determining the 5meCpG status of alleles at the Xp (RP2) and Xq (AR) chromosome arms in a single reaction. These findings are relevant and directly translatable to nonhuman primate models of XCI in which the AR CAG-repeat is monomorphic. We conducted the RP2 onshore tandem GAAA repeat assay in the naturally occurring chimeric New World monkey marmoset (Callitrichidae) and found it to be informative. The RP2 onshore tandem GAAA repeat will facilitate studies on the variable phenotypic expression of dominant and recessive X-linked diseases, epigenetic changes in twins, the physiology of aging hematopoiesis, the pathogenesis of age-related hematopoietic malignancies and the clonality of cancers in human and nonhuman primates.
Fil: Brum Machado, Filipe. Universidade de Sao Paulo; Brasil
Fil: Brum Machado, Fabricio. Universidade Estadual Do Norte Fluminense Darcy Ribeiro; Brasil
Fil: Faria, Milena Amendro. Universidade Estadual Do Norte Fluminense Darcy Ribeiro; Brasil
Fil: Lovate, Viviane Lamim. Universidade Estadual Do Norte Fluminense Darcy Ribeiro; Brasil
Fil: Alves da Silva, Antonio Francisco. Universidade Estadual Do Norte Fluminense Darcy Ribeiro; Brasil
Fil: Radic, Claudia Pamela. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: De Bras, Carlos Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Lopes Rios, Alvaro Fabricio. Universidade Estadual Do Norte Fluminense Darcy Ribeiro; Brasil
Fil: de Sousa Lopes, Susana Marina Chuva. Leiden University; Países Bajos
Fil: da Silveira, Leonardo Serafim. Universidade Estadual Do Norte Fluminense Darcy Ribeiro; Brasil
Fil: Ruiz Miranda, Carlos Ramon. Universidade Estadual Do Norte Fluminense Darcy Ribeiro; Brasil
Fil: Silveira Ramos, Ester. Universidade de Sao Paulo; Brasil
Fil: Medina-Acosta, Enrique. Universidade Estadual Do Norte Fluminense Darcy Ribeiro; Brasil
description X-chromosome inactivation (XCI) is the epigenetic transcriptional silencing of an X-chromosome during the early stages of embryonic development in female eutherian mammals. XCI assures monoallelic expression in each cell and compensation for dosage-sensitive X-linked genes between females (XX) and males (XY). DNA methylation at the carbon-5 position of the cytosine pyrimidine ring in the context of a CpG dinucleotide sequence (5meCpG) in promoter regions is a key epigeneticmarker for transcriptional gene silencing. Using computational analysis, we revealed an extragenic tandem GAAA repeat 230-bp from the landmark CpG island of the human X-linked retinitis pigmentosa 2 RP2 promoter whose 5meCpG status correlates with XCI. We used this RP2 onshore tandem GAAA repeat to develop an allele-specific 5meCpG-based PCR assay that is highly concordant with the human androgen receptor (AR) exonic tandem CAG repeat-based standard HUMARA assay in discriminating active (Xa) from inactive (Xi) X-chromosomes. The RP2 onshore tandem GAAA repeat contains neutral features that are lacking in the AR disease-linked tandem CAG repeat, is highly polymorphic (heterozygosity rates approximately 0.8) and shows minimal variation in the Xa/Xi ratio. The combined informativeness of RP2/AR is approximately 0.97, and this assay excels at determining the 5meCpG status of alleles at the Xp (RP2) and Xq (AR) chromosome arms in a single reaction. These findings are relevant and directly translatable to nonhuman primate models of XCI in which the AR CAG-repeat is monomorphic. We conducted the RP2 onshore tandem GAAA repeat assay in the naturally occurring chimeric New World monkey marmoset (Callitrichidae) and found it to be informative. The RP2 onshore tandem GAAA repeat will facilitate studies on the variable phenotypic expression of dominant and recessive X-linked diseases, epigenetic changes in twins, the physiology of aging hematopoiesis, the pathogenesis of age-related hematopoietic malignancies and the clonality of cancers in human and nonhuman primates.
publishDate 2014
dc.date.none.fl_str_mv 2014-07
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/11336/29456
Brum Machado, Filipe; Brum Machado, Fabricio; Faria, Milena Amendro; Lovate, Viviane Lamim; Alves da Silva, Antonio Francisco; et al.; 5meCpG Epigenetic Marks Neighboring a Primate-Conserved Core Promoter Short Tandem Repeat Indicate X-Chromosome Inactivation; Public Library of Science; Plos One; 9; 7-2014; 1-13
1932-6203
CONICET Digital
CONICET
url http://hdl.handle.net/11336/29456
identifier_str_mv Brum Machado, Filipe; Brum Machado, Fabricio; Faria, Milena Amendro; Lovate, Viviane Lamim; Alves da Silva, Antonio Francisco; et al.; 5meCpG Epigenetic Marks Neighboring a Primate-Conserved Core Promoter Short Tandem Repeat Indicate X-Chromosome Inactivation; Public Library of Science; Plos One; 9; 7-2014; 1-13
1932-6203
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1371/journal.pone.0103714
info:eu-repo/semantics/altIdentifier/url/http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0103714
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
dc.publisher.none.fl_str_mv Public Library of Science
publisher.none.fl_str_mv Public Library of Science
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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