Data/hora: 16/06/2024 14:51:57

Provedor de dados: 	74	
País: 	Brazil	
Título: 	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	
Autores: 	Erdem,Gokce Celikyapi; Erdemir,Sule; Abaci,Irem; Aydin,Asli K. Kirectepe; Everest,Elif; Turanli,Eda Tahir.	
Data: 	2017-09-01	
Ano: 	2017	
Palavras-chave: 	Exon methylation; MEFV; Pyrin; Alternative splicing; Inflammation.	
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 &lt; 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.	
Tipo: 	Info:eu-repo/semantics/article	
Idioma: 	Inglês	
Identificador: 	http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1415-47572017000400688	
Editor: 	Sociedade Brasileira de Genética	
Relação: 	10.1590/1678-4685-gmb-2016-0234	
Formato: 	text/html	
Fonte: 	Genetics and Molecular Biology  v.40 n.3 2017	
Fonte: 	info:eu-repo/semantics/openAccess