Maternal 5mCpG Imprints at the PARD6G-AS1 and GCSAML Differentially Methylated Regions Are Decoupled From Parent-of-Origin Expression Effects in Multiple Human Tissues
A hallmark of imprinted genes in mammals is the occurrence of parent-of-origin-dependent asymmetry of DNA cytosine methylation (5mC) of alleles at CpG islands (CGIs) in their promoter regions. This 5mCpG asymmetry between the parental alleles creates allele-specific imprinted differentially methylat...
| Main Authors: | , , , , , , , , , , , , , , |
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| Formato: | Artigo |
| Idioma: | English |
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Frontiers Media S.A.
2018-03-01
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| Colecção: | Frontiers in Genetics |
| Assuntos: | |
| Acesso em linha: | http://journal.frontiersin.org/article/10.3389/fgene.2018.00036/full |
| _version_ | 1828165096862384128 |
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| author | Graziela de Sá Machado Araújo Ronaldo da Silva Francisco Junior Ronaldo da Silva Francisco Junior Cristina dos Santos Ferreira Pedro Thyago Mozer Rodrigues Douglas Terra Machado Thais Louvain de Souza Thais Louvain de Souza Jozimara Teixeira de Souza Cleiton Figueiredo Osorio da Silva Antônio Francisco Alves da Silva Claudia Caixeta Franco Andrade Claudia Caixeta Franco Andrade Alan Tardin da Silva Victor Ramos Ana Beatriz Garcia Filipe Brum Machado Enrique Medina-Acosta |
| author_facet | Graziela de Sá Machado Araújo Ronaldo da Silva Francisco Junior Ronaldo da Silva Francisco Junior Cristina dos Santos Ferreira Pedro Thyago Mozer Rodrigues Douglas Terra Machado Thais Louvain de Souza Thais Louvain de Souza Jozimara Teixeira de Souza Cleiton Figueiredo Osorio da Silva Antônio Francisco Alves da Silva Claudia Caixeta Franco Andrade Claudia Caixeta Franco Andrade Alan Tardin da Silva Victor Ramos Ana Beatriz Garcia Filipe Brum Machado Enrique Medina-Acosta |
| author_sort | Graziela de Sá Machado Araújo |
| collection | DOAJ |
| description | A hallmark of imprinted genes in mammals is the occurrence of parent-of-origin-dependent asymmetry of DNA cytosine methylation (5mC) of alleles at CpG islands (CGIs) in their promoter regions. This 5mCpG asymmetry between the parental alleles creates allele-specific imprinted differentially methylated regions (iDMRs). iDMRs are often coupled to the transcriptional repression of the methylated allele and the activation of the unmethylated allele in a tissue-specific, developmental-stage-specific and/or isoform-specific fashion. iDMRs function as regulatory platforms, built through the recruitment of chemical modifications to histones to achieve differential, parent-of-origin-dependent chromatin segmentation states. Here, we used a comparative computational data mining approach to identify 125 novel constitutive candidate iDMRs that integrate the maximal number of allele-specific methylation region records overlapping CGIs in human methylomes. Twenty-nine candidate iDMRs display gametic 5mCpG asymmetry, and another 96 are candidate secondary iDMRs. We established the maternal origin of the 5mCpG imprints of one gametic (PARD6G-AS1) and one secondary (GCSAML) iDMRs. We also found a constitutively hemimethylated, nonimprinted domain at the PWWP2AP1 promoter CGI with oocyte-derived methylation asymmetry. Given that the 5mCpG level at the iDMRs is not a sufficient criterion to predict active or silent locus states and that iDMRs can regulate genes from a distance of more than 1 Mb, we used RNA-Seq experiments from the Genotype-Tissue Expression project and public archives to assess the transcriptional expression profiles of SNPs across 4.6 Mb spans around the novel maternal iDMRs. We showed that PARD6G-AS1 and GCSAML are expressed biallelically in multiple tissues. We found evidence of tissue-specific monoallelic expression of ZNF124 and OR2L13, located 363 kb upstream and 419 kb downstream, respectively, of the GCSAML iDMR. We hypothesize that the GCSAML iDMR regulates the tissue-specific, monoallelic expression of ZNF124 but not of OR2L13. We annotated the non-coding epigenomic marks in the two maternal iDMRs using data from the Roadmap Epigenomics project and showed that the PARD6G-AS1 and GCSAML iDMRs achieve contrasting activation and repression chromatin segmentations. Lastly, we found that the maternal 5mCpG imprints are perturbed in several hematopoietic cancers. We conclude that the maternal 5mCpG imprints at PARD6G-AS1 and GCSAML iDMRs are decoupled from parent-of-origin transcriptional expression effects in multiple tissues. |
| first_indexed | 2024-04-12T01:37:55Z |
| format | Article |
| id | doaj.art-fd9af73e6f9e49efaae2bc8d0af70868 |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-04-12T01:37:55Z |
| publishDate | 2018-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj.art-fd9af73e6f9e49efaae2bc8d0af708682022-12-22T03:53:17ZengFrontiers Media S.A.Frontiers in Genetics1664-80212018-03-01910.3389/fgene.2018.00036314929Maternal 5mCpG Imprints at the PARD6G-AS1 and GCSAML Differentially Methylated Regions Are Decoupled From Parent-of-Origin Expression Effects in Multiple Human TissuesGraziela de Sá Machado Araújo0Ronaldo da Silva Francisco Junior1Ronaldo da Silva Francisco Junior2Cristina dos Santos Ferreira3Pedro Thyago Mozer Rodrigues4Douglas Terra Machado5Thais Louvain de Souza6Thais Louvain de Souza7Jozimara Teixeira de Souza8Cleiton Figueiredo Osorio da Silva9Antônio Francisco Alves da Silva10Claudia Caixeta Franco Andrade11Claudia Caixeta Franco Andrade12Alan Tardin da Silva13Victor Ramos14Ana Beatriz Garcia15Filipe Brum Machado16Enrique Medina-Acosta17Núcleo de Diagnóstico e Investigação Molecular, Laboratório de Biotecnologia, Centro de Biociências e Biotecnologia, Universidade Estadual do Norte Fluminense Darcy Ribeiro, Campos dos Goytacazes, BrazilNúcleo de Diagnóstico e Investigação Molecular, Laboratório de Biotecnologia, Centro de Biociências e Biotecnologia, Universidade Estadual do Norte Fluminense Darcy Ribeiro, Campos dos Goytacazes, BrazilLaboratório Nacional de Computação Científica, Petrópolis, BrazilNúcleo de Diagnóstico e Investigação Molecular, Laboratório de Biotecnologia, Centro de Biociências e Biotecnologia, Universidade Estadual do Norte Fluminense Darcy Ribeiro, Campos dos Goytacazes, BrazilNúcleo de Diagnóstico e Investigação Molecular, Laboratório de Biotecnologia, Centro de Biociências e Biotecnologia, Universidade Estadual do Norte Fluminense Darcy Ribeiro, Campos dos Goytacazes, BrazilNúcleo de Diagnóstico e Investigação Molecular, Laboratório de Biotecnologia, Centro de Biociências e Biotecnologia, Universidade Estadual do Norte Fluminense Darcy Ribeiro, Campos dos Goytacazes, BrazilNúcleo de Diagnóstico e Investigação Molecular, Laboratório de Biotecnologia, Centro de Biociências e Biotecnologia, Universidade Estadual do Norte Fluminense Darcy Ribeiro, Campos dos Goytacazes, BrazilFaculdade de Medicina de Campos, Campos dos Goytacazes, BrazilNúcleo de Diagnóstico e Investigação Molecular, Laboratório de Biotecnologia, Centro de Biociências e Biotecnologia, Universidade Estadual do Norte Fluminense Darcy Ribeiro, Campos dos Goytacazes, BrazilNúcleo de Diagnóstico e Investigação Molecular, Laboratório de Biotecnologia, Centro de Biociências e Biotecnologia, Universidade Estadual do Norte Fluminense Darcy Ribeiro, Campos dos Goytacazes, BrazilNúcleo de Diagnóstico e Investigação Molecular, Laboratório de Biotecnologia, Centro de Biociências e Biotecnologia, Universidade Estadual do Norte Fluminense Darcy Ribeiro, Campos dos Goytacazes, BrazilNúcleo de Diagnóstico e Investigação Molecular, Laboratório de Biotecnologia, Centro de Biociências e Biotecnologia, Universidade Estadual do Norte Fluminense Darcy Ribeiro, Campos dos Goytacazes, BrazilFaculdade Metropolitana São Carlos, Bom Jesus do Itabapoana, BrazilNúcleo de Diagnóstico e Investigação Molecular, Laboratório de Biotecnologia, Centro de Biociências e Biotecnologia, Universidade Estadual do Norte Fluminense Darcy Ribeiro, Campos dos Goytacazes, BrazilFaculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, BrazilNúcleo de Diagnóstico e Investigação Molecular, Laboratório de Biotecnologia, Centro de Biociências e Biotecnologia, Universidade Estadual do Norte Fluminense Darcy Ribeiro, Campos dos Goytacazes, BrazilNúcleo de Diagnóstico e Investigação Molecular, Laboratório de Biotecnologia, Centro de Biociências e Biotecnologia, Universidade Estadual do Norte Fluminense Darcy Ribeiro, Campos dos Goytacazes, BrazilNúcleo de Diagnóstico e Investigação Molecular, Laboratório de Biotecnologia, Centro de Biociências e Biotecnologia, Universidade Estadual do Norte Fluminense Darcy Ribeiro, Campos dos Goytacazes, BrazilA hallmark of imprinted genes in mammals is the occurrence of parent-of-origin-dependent asymmetry of DNA cytosine methylation (5mC) of alleles at CpG islands (CGIs) in their promoter regions. This 5mCpG asymmetry between the parental alleles creates allele-specific imprinted differentially methylated regions (iDMRs). iDMRs are often coupled to the transcriptional repression of the methylated allele and the activation of the unmethylated allele in a tissue-specific, developmental-stage-specific and/or isoform-specific fashion. iDMRs function as regulatory platforms, built through the recruitment of chemical modifications to histones to achieve differential, parent-of-origin-dependent chromatin segmentation states. Here, we used a comparative computational data mining approach to identify 125 novel constitutive candidate iDMRs that integrate the maximal number of allele-specific methylation region records overlapping CGIs in human methylomes. Twenty-nine candidate iDMRs display gametic 5mCpG asymmetry, and another 96 are candidate secondary iDMRs. We established the maternal origin of the 5mCpG imprints of one gametic (PARD6G-AS1) and one secondary (GCSAML) iDMRs. We also found a constitutively hemimethylated, nonimprinted domain at the PWWP2AP1 promoter CGI with oocyte-derived methylation asymmetry. Given that the 5mCpG level at the iDMRs is not a sufficient criterion to predict active or silent locus states and that iDMRs can regulate genes from a distance of more than 1 Mb, we used RNA-Seq experiments from the Genotype-Tissue Expression project and public archives to assess the transcriptional expression profiles of SNPs across 4.6 Mb spans around the novel maternal iDMRs. We showed that PARD6G-AS1 and GCSAML are expressed biallelically in multiple tissues. We found evidence of tissue-specific monoallelic expression of ZNF124 and OR2L13, located 363 kb upstream and 419 kb downstream, respectively, of the GCSAML iDMR. We hypothesize that the GCSAML iDMR regulates the tissue-specific, monoallelic expression of ZNF124 but not of OR2L13. We annotated the non-coding epigenomic marks in the two maternal iDMRs using data from the Roadmap Epigenomics project and showed that the PARD6G-AS1 and GCSAML iDMRs achieve contrasting activation and repression chromatin segmentations. Lastly, we found that the maternal 5mCpG imprints are perturbed in several hematopoietic cancers. We conclude that the maternal 5mCpG imprints at PARD6G-AS1 and GCSAML iDMRs are decoupled from parent-of-origin transcriptional expression effects in multiple tissues.http://journal.frontiersin.org/article/10.3389/fgene.2018.00036/fullPARD6G-AS1GCSAMLGRB10ZNF124OR2L13LOC284240 |
| spellingShingle | Graziela de Sá Machado Araújo Ronaldo da Silva Francisco Junior Ronaldo da Silva Francisco Junior Cristina dos Santos Ferreira Pedro Thyago Mozer Rodrigues Douglas Terra Machado Thais Louvain de Souza Thais Louvain de Souza Jozimara Teixeira de Souza Cleiton Figueiredo Osorio da Silva Antônio Francisco Alves da Silva Claudia Caixeta Franco Andrade Claudia Caixeta Franco Andrade Alan Tardin da Silva Victor Ramos Ana Beatriz Garcia Filipe Brum Machado Enrique Medina-Acosta Maternal 5mCpG Imprints at the PARD6G-AS1 and GCSAML Differentially Methylated Regions Are Decoupled From Parent-of-Origin Expression Effects in Multiple Human Tissues Frontiers in Genetics PARD6G-AS1 GCSAML GRB10 ZNF124 OR2L13 LOC284240 |
| title | Maternal 5mCpG Imprints at the PARD6G-AS1 and GCSAML Differentially Methylated Regions Are Decoupled From Parent-of-Origin Expression Effects in Multiple Human Tissues |
| title_full | Maternal 5mCpG Imprints at the PARD6G-AS1 and GCSAML Differentially Methylated Regions Are Decoupled From Parent-of-Origin Expression Effects in Multiple Human Tissues |
| title_fullStr | Maternal 5mCpG Imprints at the PARD6G-AS1 and GCSAML Differentially Methylated Regions Are Decoupled From Parent-of-Origin Expression Effects in Multiple Human Tissues |
| title_full_unstemmed | Maternal 5mCpG Imprints at the PARD6G-AS1 and GCSAML Differentially Methylated Regions Are Decoupled From Parent-of-Origin Expression Effects in Multiple Human Tissues |
| title_short | Maternal 5mCpG Imprints at the PARD6G-AS1 and GCSAML Differentially Methylated Regions Are Decoupled From Parent-of-Origin Expression Effects in Multiple Human Tissues |
| title_sort | maternal 5mcpg imprints at the pard6g as1 and gcsaml differentially methylated regions are decoupled from parent of origin expression effects in multiple human tissues |
| topic | PARD6G-AS1 GCSAML GRB10 ZNF124 OR2L13 LOC284240 |
| url | http://journal.frontiersin.org/article/10.3389/fgene.2018.00036/full |
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