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
Autor(a) principal: | |
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Data de Publicação: | 2017 |
Outros Autores: | , , , , |
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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Genetics and Molecular Biology |
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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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1752122387633012736 |