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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Stability of XIST repression in relation to genomic imprinting following global genome demethylation in a human cell line

Texto completo
Autor(es):
de Araujo, E. S. S. [1, 2] ; Vasques, L. R. [1] ; Stabellini, R. [1, 2] ; Krepischi, A. C. V. [1, 2] ; Pereira, L. V. [1]
Número total de Autores: 5
Afiliação do(s) autor(es):
[1] Univ Sao Paulo, Inst Biociencias, Dept Genet & Biol Evolut, Sao Paulo - Brazil
[2] AC Camargo Canc Ctr, Ctr Int Pesquisa, Sao Paulo - Brazil
Número total de Afiliações: 2
Tipo de documento: Artigo Científico
Fonte: Brazilian Journal of Medical and Biological Research; v. 47, n. 12, p. 1029-1035, DEC 2014.
Citações Web of Science: 0
Resumo

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. (AU)

Processo FAPESP: 08/07370-0 - Análise comparativa do controle epigenético em células humanas normais e transformadas
Beneficiário:Érica Sara Souza de Araújo
Linha de fomento: Bolsas no Brasil - Mestrado