Alternatively spliced MEFV transcript lacking exon 2 and its protein isoform pyrin-2d implies an epigenetic regulation of the gene in inflammatory cell culture models

Detalhes bibliográficos
Autor(a) principal: Erdem,Gokce Celikyapi
Data de Publicação: 2017
Outros Autores: Erdemir,Sule, Abaci,Irem, Aydin,Asli K. Kirectepe, Everest,Elif, Turanli,Eda Tahir
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Genetics and Molecular Biology
Texto Completo: http://old.scielo.br/scielo.php?script=sci_arttext&pid=S1415-47572017000400688
Resumo: Abstract The function of gene body DNA methylation in alternative splicing, and its relation to disease pathogenesis is not fully elucidated. The gene for familial Mediterranean fever (MEFV) encodes the pyrin protein and contains a 998 bp CpG island, covering the second exon, which is differentially methylated in FMF patients compared to healthy controls. Our further observation of increased exon 2-spliced MEFV transcript in leukocytes of FMF patients provoked us to test the role of exon methylation in alternative splicing using inflammatory cell culture models. First, in vitro exon methylation triggered an increased level of exon 2 exclusion using a splicing cassette in a promyelocytic leukemia cell line (HL-60). HL-60 cells subjected to methylating and demethylating agents, as well as cells differentiated to neutrophil-like cells, exhibited different levels of spliced/unspliced transcripts. We observed increased levels of spliced transcripts in neutrophil-like (p = 0.0005), activated (p = 0.0034) and methylated cells (p < 0.0001), whereas decreased levels in demethylated cells (p = 0.0126) compared to control untreated HL-60 cells. We also showed that the protein isoform of pyrin lacking the exon 2 has an adverse subcellular localization in neutrophil-like cells. Therefore, it remains in the cytoplasm rather than the nucleus. This may point to an epigenetic involvement in an important inflammatory gene.
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spelling Alternatively spliced MEFV transcript lacking exon 2 and its protein isoform pyrin-2d implies an epigenetic regulation of the gene in inflammatory cell culture modelsExon methylationMEFVpyrinalternative splicinginflammationAbstract The function of gene body DNA methylation in alternative splicing, and its relation to disease pathogenesis is not fully elucidated. The gene for familial Mediterranean fever (MEFV) encodes the pyrin protein and contains a 998 bp CpG island, covering the second exon, which is differentially methylated in FMF patients compared to healthy controls. Our further observation of increased exon 2-spliced MEFV transcript in leukocytes of FMF patients provoked us to test the role of exon methylation in alternative splicing using inflammatory cell culture models. First, in vitro exon methylation triggered an increased level of exon 2 exclusion using a splicing cassette in a promyelocytic leukemia cell line (HL-60). HL-60 cells subjected to methylating and demethylating agents, as well as cells differentiated to neutrophil-like cells, exhibited different levels of spliced/unspliced transcripts. We observed increased levels of spliced transcripts in neutrophil-like (p = 0.0005), activated (p = 0.0034) and methylated cells (p < 0.0001), whereas decreased levels in demethylated cells (p = 0.0126) compared to control untreated HL-60 cells. We also showed that the protein isoform of pyrin lacking the exon 2 has an adverse subcellular localization in neutrophil-like cells. Therefore, it remains in the cytoplasm rather than the nucleus. This may point to an epigenetic involvement in an important inflammatory gene.Sociedade Brasileira de Genética2017-09-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersiontext/htmlhttp://old.scielo.br/scielo.php?script=sci_arttext&pid=S1415-47572017000400688Genetics and Molecular Biology v.40 n.3 2017reponame:Genetics and Molecular Biologyinstname:Sociedade Brasileira de Genética (SBG)instacron:SBG10.1590/1678-4685-gmb-2016-0234info:eu-repo/semantics/openAccessErdem,Gokce CelikyapiErdemir,SuleAbaci,IremAydin,Asli K. KirectepeEverest,ElifTuranli,Eda Tahireng2017-09-01T00:00:00Zoai:scielo:S1415-47572017000400688Revistahttp://www.gmb.org.br/ONGhttps://old.scielo.br/oai/scielo-oai.php||editor@gmb.org.br1678-46851415-4757opendoar:2017-09-01T00:00Genetics and Molecular Biology - Sociedade Brasileira de Genética (SBG)false
dc.title.none.fl_str_mv Alternatively spliced MEFV transcript lacking exon 2 and its protein isoform pyrin-2d implies an epigenetic regulation of the gene in inflammatory cell culture models
title Alternatively spliced MEFV transcript lacking exon 2 and its protein isoform pyrin-2d implies an epigenetic regulation of the gene in inflammatory cell culture models
spellingShingle Alternatively spliced MEFV transcript lacking exon 2 and its protein isoform pyrin-2d implies an epigenetic regulation of the gene in inflammatory cell culture models
Erdem,Gokce Celikyapi
Exon methylation
MEFV
pyrin
alternative splicing
inflammation
title_short Alternatively spliced MEFV transcript lacking exon 2 and its protein isoform pyrin-2d implies an epigenetic regulation of the gene in inflammatory cell culture models
title_full Alternatively spliced MEFV transcript lacking exon 2 and its protein isoform pyrin-2d implies an epigenetic regulation of the gene in inflammatory cell culture models
title_fullStr Alternatively spliced MEFV transcript lacking exon 2 and its protein isoform pyrin-2d implies an epigenetic regulation of the gene in inflammatory cell culture models
title_full_unstemmed Alternatively spliced MEFV transcript lacking exon 2 and its protein isoform pyrin-2d implies an epigenetic regulation of the gene in inflammatory cell culture models
title_sort Alternatively spliced MEFV transcript lacking exon 2 and its protein isoform pyrin-2d implies an epigenetic regulation of the gene in inflammatory cell culture models
author Erdem,Gokce Celikyapi
author_facet Erdem,Gokce Celikyapi
Erdemir,Sule
Abaci,Irem
Aydin,Asli K. Kirectepe
Everest,Elif
Turanli,Eda Tahir
author_role author
author2 Erdemir,Sule
Abaci,Irem
Aydin,Asli K. Kirectepe
Everest,Elif
Turanli,Eda Tahir
author2_role author
author
author
author
author
dc.contributor.author.fl_str_mv Erdem,Gokce Celikyapi
Erdemir,Sule
Abaci,Irem
Aydin,Asli K. Kirectepe
Everest,Elif
Turanli,Eda Tahir
dc.subject.por.fl_str_mv Exon methylation
MEFV
pyrin
alternative splicing
inflammation
topic Exon methylation
MEFV
pyrin
alternative splicing
inflammation
description Abstract The function of gene body DNA methylation in alternative splicing, and its relation to disease pathogenesis is not fully elucidated. The gene for familial Mediterranean fever (MEFV) encodes the pyrin protein and contains a 998 bp CpG island, covering the second exon, which is differentially methylated in FMF patients compared to healthy controls. Our further observation of increased exon 2-spliced MEFV transcript in leukocytes of FMF patients provoked us to test the role of exon methylation in alternative splicing using inflammatory cell culture models. First, in vitro exon methylation triggered an increased level of exon 2 exclusion using a splicing cassette in a promyelocytic leukemia cell line (HL-60). HL-60 cells subjected to methylating and demethylating agents, as well as cells differentiated to neutrophil-like cells, exhibited different levels of spliced/unspliced transcripts. We observed increased levels of spliced transcripts in neutrophil-like (p = 0.0005), activated (p = 0.0034) and methylated cells (p < 0.0001), whereas decreased levels in demethylated cells (p = 0.0126) compared to control untreated HL-60 cells. We also showed that the protein isoform of pyrin lacking the exon 2 has an adverse subcellular localization in neutrophil-like cells. Therefore, it remains in the cytoplasm rather than the nucleus. This may point to an epigenetic involvement in an important inflammatory gene.
publishDate 2017
dc.date.none.fl_str_mv 2017-09-01
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://old.scielo.br/scielo.php?script=sci_arttext&pid=S1415-47572017000400688
url http://old.scielo.br/scielo.php?script=sci_arttext&pid=S1415-47572017000400688
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 10.1590/1678-4685-gmb-2016-0234
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv text/html
dc.publisher.none.fl_str_mv Sociedade Brasileira de Genética
publisher.none.fl_str_mv Sociedade Brasileira de Genética
dc.source.none.fl_str_mv Genetics and Molecular Biology v.40 n.3 2017
reponame:Genetics and Molecular Biology
instname:Sociedade Brasileira de Genética (SBG)
instacron:SBG
instname_str Sociedade Brasileira de Genética (SBG)
instacron_str SBG
institution SBG
reponame_str Genetics and Molecular Biology
collection Genetics and Molecular Biology
repository.name.fl_str_mv Genetics and Molecular Biology - Sociedade Brasileira de Genética (SBG)
repository.mail.fl_str_mv ||editor@gmb.org.br
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