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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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Author(s):
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]
Total Authors: 5
Affiliation:
[1] Univ Sao Paulo, Inst Biociencias, Dept Genet & Biol Evolut, Sao Paulo - Brazil
[2] AC Camargo Canc Ctr, Ctr Int Pesquisa, Sao Paulo - Brazil
Total Affiliations: 2
Document type: Journal article
Source: Brazilian Journal of Medical and Biological Research; v. 47, n. 12, p. 1029-1035, DEC 2014.
Web of Science Citations: 0
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 thatXIST 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 ofXIST 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)

FAPESP's process: 08/07370-0 - Comparative analysis of the epigenetic control in normal and transformed human cells.
Grantee:Érica Sara Souza de Araújo
Support Opportunities: Scholarships in Brazil - Master