Stability of XIST repression in relation to genomic imprinting following global genome demethylation in a human cell line
Rev. bras. pesqui. méd. biol
; Braz. j. med. biol. res;47(12): 1029-1035, 12/2014. graf
Article
em En
| LILACS
| ID: lil-727661
Biblioteca responsável:
BR1.1
ABSTRACT
DNA methylation is essential in X chromosome inactivation and genomic imprinting, maintaining repression of XIST in the active X chromosome and monoallelic repression of imprinted genes. Disruption of the DNA methyltransferase genes DNMT1 and DNMT3B in the HCT116 cell line (DKO cells) leads to global DNA hypomethylation and biallelic expression of the imprinted gene IGF2 but does not lead to reactivation of XIST expression, suggesting that XIST repression is due to a more stable epigenetic mark than imprinting. To test this hypothesis, we induced acute hypomethylation in HCT116 cells by 5-aza-2′-deoxycytidine (5-aza-CdR) treatment (HCT116-5-aza-CdR) and compared that to DKO cells, evaluating DNA methylation by microarray and monitoring the expression of XIST and imprinted genes IGF2, H19, and PEG10. Whereas imprinted genes showed biallelic expression in HCT116-5-aza-CdR and DKO cells, the XIST locus was hypomethylated and weakly expressed only under acute hypomethylation conditions, indicating the importance of XIST repression in the active X to cell survival. Given that DNMT3A is the only active DNMT in DKO cells, it may be responsible for ensuring the repression of XIST in those cells. Taken together, our data suggest that XIST repression is more tightly controlled than genomic imprinting and, at least in part, is due to DNMT3A.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
LILACS
Assunto principal:
Fator de Crescimento Insulin-Like II
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Genoma Humano
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Genoma
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Impressão Genômica
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Metilação de DNA
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RNA Longo não Codificante
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Repressão Epigenética
Limite:
Humans
Idioma:
En
Revista:
Braz J Med Biol Res
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Braz. j. med. biol. res
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Braz. j. med. biol. res. (Online)
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Brazilian journal of medical and biological research
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Brazilian journal of medical and biological research (Impresso)
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Rev. bras. pesqui. méd. biol
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Revista brasileira de pesquisas médicas e biológicas
Assunto da revista:
BIOLOGIA
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MEDICINA
Ano de publicação:
2014
Tipo de documento:
Article
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Project document
País de afiliação:
Brasil