Histone deacetylase inhibition modulates histone acetylation at gene promoter regions and affects genome-wide gene transcription in Schistosoma mansoni.
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2017 |
| Outros Autores: | , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Institucional da FIOCRUZ (ARCA) |
| Texto Completo: | https://www.arca.fiocruz.br/handle/icict/26487 |
Resumo: | Universidade de São Paulo, São Paulo. Instituto de Química. Departamento de Bioquímica. São Paulo, SP, Brazil/Instituto Butantan. São Paulo, SP, Brazil |
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Anderson, LetíciaGomes, Monete RajãoSilva, Lucas Ferreira daPereira, Adriana da Silva AndradeMourão, Marina MoraesRomier, ChristophePierce, Raymond JohnAlmeida, Sergio Verjovski2018-05-18T17:35:23Z2018-05-18T17:35:23Z2017ANDERSON, Leticia et al. Histone deacetylase inhibition modulates histone acetylation at gene promoter regions and affects genome-wide gene transcription in Schistosoma mansoni. PLoS Negl Trop Dis., v. 11, n. 4, art.e0005539, 2017.1935-2727https://www.arca.fiocruz.br/handle/icict/2648710.1371/journal.pntd.0005539engPublic Library of ScienceHistonesexpressão geneticareplicação de DNASchistosoma mansoniHistonesGene expressionSchistosoma mansoniDNA replicationGene ontologiesDNA transcriptionChromatinPromoter regionsHistone deacetylase inhibition modulates histone acetylation at gene promoter regions and affects genome-wide gene transcription in Schistosoma mansoni.info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleUniversidade de São Paulo, São Paulo. Instituto de Química. Departamento de Bioquímica. São Paulo, SP, Brazil/Instituto Butantan. São Paulo, SP, BrazilInstituto Butantan. São Paulo, SP, BrazilUniversidade de São Paulo, São Paulo. Instituto de Química. Departamento de Bioquímica. São Paulo, SP, Brazil/Instituto Butantan. São Paulo, SP, BrazilUniversidade de São Paulo, São Paulo. Instituto de Química. Departamento de Bioquímica. São Paulo, SP, Brazil/Instituto Butantan. São Paulo, SP, BrazilFundação Oswaldo Cruz. Instituto René Rachou. Grupo de Helmintologia e Malacologia Médica. Belo Horizonte, MG, BrazilDépartement de Biologie Structurale Intégrative. Institut de Génétique et Biologie Moléculaire et Cellulaire (IGBMC). Université de Strasbourg. CNRS, INSERM, Illkirch, FranceUniversité de Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, Centre d'Infection et d'Immunité de Lille, Lille, FranceUniversidade de São Paulo, São Paulo. Instituto de Química. Departamento de Bioquímica. São Paulo, SP, Brazil/Instituto Butantan. São Paulo, SP, BrazilBackground: Schistosomiasis is a parasitic disease infecting hundreds of millions of people worldwide. Treatment depends on a single drug, praziquantel, which kills the Schistosoma spp. parasite only at the adult stage. HDAC inhibitors (HDACi) such as Trichostatin A (TSA) induce parasite mortality in vitro (schistosomula and adult worms), however the downstream effects of histone hyperacetylation on the parasite are not known. Methodology/Principal findings: TSA treatment of adult worms in vitro increased histone acetylation at H3K9ac and H3K14ac, which are transcription activation marks, not affecting the unrelated transcription repression mark H3K27me3. We investigated the effect of TSA HDACi on schistosomula gene expression at three different time points, finding a marked genome-wide change in the transcriptome profile. Gene transcription activity was correlated with changes on the chromatin acetylation mark at gene promoter regions. Moreover, combining expression data with ChIP-Seq public data for schistosomula, we found that differentially expressed genes having the H3K4me3 mark at their promoter region in general showed transcription activation upon HDACi treatment, compared with those without the mark, which showed transcription down-regulation. Affected genes are enriched for DNA replication processes, most of them being up-regulated. Twenty out of 22 genes encoding proteins involved in reducing reactive oxygen species accumulation were down-regulated. Dozens of genes encoding proteins with histone reader motifs were changed, including SmEED from the PRC2 complex. We targeted SmEZH2 methyltransferase PRC2 component with a new EZH2 inhibitor (GSK343) and showed a synergistic effect with TSA, significantly increasing schistosomula mortality. Conclusions/Significance: Genome-wide gene expression analyses have identified important pathways and cellular functions that were affected and may explain the schistosomicidal effect of TSA HDACi. The change in expression of dozens of histone reader genes involved in regulation of the epigenetic program in S. mansoni can be used as a starting point to look for possible novel schistosomicidal targets.info:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-83082https://www.arca.fiocruz.br/bitstream/icict/26487/1/license.txt9193a7c197bc67acd023525e72a03240MD51ORIGINALHistone deacetylase inhibition modulates histone.pdfHistone deacetylase inhibition modulates histone.pdfapplication/pdf3220587https://www.arca.fiocruz.br/bitstream/icict/26487/2/Histone%20deacetylase%20inhibition%20modulates%20histone.pdff2643d2fdac247194e310a43448179e0MD52TEXTHistone deacetylase inhibition modulates histone.pdf.txtHistone deacetylase inhibition modulates histone.pdf.txtExtracted 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| dc.title.pt_BR.fl_str_mv |
Histone deacetylase inhibition modulates histone acetylation at gene promoter regions and affects genome-wide gene transcription in Schistosoma mansoni. |
| title |
Histone deacetylase inhibition modulates histone acetylation at gene promoter regions and affects genome-wide gene transcription in Schistosoma mansoni. |
| spellingShingle |
Histone deacetylase inhibition modulates histone acetylation at gene promoter regions and affects genome-wide gene transcription in Schistosoma mansoni. Anderson, Letícia Histones expressão genetica replicação de DNA Schistosoma mansoni Histones Gene expression Schistosoma mansoni DNA replication Gene ontologies DNA transcription Chromatin Promoter regions |
| title_short |
Histone deacetylase inhibition modulates histone acetylation at gene promoter regions and affects genome-wide gene transcription in Schistosoma mansoni. |
| title_full |
Histone deacetylase inhibition modulates histone acetylation at gene promoter regions and affects genome-wide gene transcription in Schistosoma mansoni. |
| title_fullStr |
Histone deacetylase inhibition modulates histone acetylation at gene promoter regions and affects genome-wide gene transcription in Schistosoma mansoni. |
| title_full_unstemmed |
Histone deacetylase inhibition modulates histone acetylation at gene promoter regions and affects genome-wide gene transcription in Schistosoma mansoni. |
| title_sort |
Histone deacetylase inhibition modulates histone acetylation at gene promoter regions and affects genome-wide gene transcription in Schistosoma mansoni. |
| author |
Anderson, Letícia |
| author_facet |
Anderson, Letícia Gomes, Monete Rajão Silva, Lucas Ferreira da Pereira, Adriana da Silva Andrade Mourão, Marina Moraes Romier, Christophe Pierce, Raymond John Almeida, Sergio Verjovski |
| author_role |
author |
| author2 |
Gomes, Monete Rajão Silva, Lucas Ferreira da Pereira, Adriana da Silva Andrade Mourão, Marina Moraes Romier, Christophe Pierce, Raymond John Almeida, Sergio Verjovski |
| author2_role |
author author author author author author author |
| dc.contributor.author.fl_str_mv |
Anderson, Letícia Gomes, Monete Rajão Silva, Lucas Ferreira da Pereira, Adriana da Silva Andrade Mourão, Marina Moraes Romier, Christophe Pierce, Raymond John Almeida, Sergio Verjovski |
| dc.subject.other.pt_BR.fl_str_mv |
Histones expressão genetica replicação de DNA Schistosoma mansoni |
| topic |
Histones expressão genetica replicação de DNA Schistosoma mansoni Histones Gene expression Schistosoma mansoni DNA replication Gene ontologies DNA transcription Chromatin Promoter regions |
| dc.subject.en.pt_BR.fl_str_mv |
Histones Gene expression Schistosoma mansoni DNA replication Gene ontologies DNA transcription Chromatin Promoter regions |
| description |
Universidade de São Paulo, São Paulo. Instituto de Química. Departamento de Bioquímica. São Paulo, SP, Brazil/Instituto Butantan. São Paulo, SP, Brazil |
| publishDate |
2017 |
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2017 |
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2018-05-18T17:35:23Z |
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2018-05-18T17:35:23Z |
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ANDERSON, Leticia et al. Histone deacetylase inhibition modulates histone acetylation at gene promoter regions and affects genome-wide gene transcription in Schistosoma mansoni. PLoS Negl Trop Dis., v. 11, n. 4, art.e0005539, 2017. |
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https://www.arca.fiocruz.br/handle/icict/26487 |
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1935-2727 |
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10.1371/journal.pntd.0005539 |
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ANDERSON, Leticia et al. Histone deacetylase inhibition modulates histone acetylation at gene promoter regions and affects genome-wide gene transcription in Schistosoma mansoni. PLoS Negl Trop Dis., v. 11, n. 4, art.e0005539, 2017. 1935-2727 10.1371/journal.pntd.0005539 |
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