Tissue and cancer-specific expression of DIEXF is epigenetically mediated by an Alu repeat.
Por:
Martín B, Pappa S, Díez-Villanueva A, Mallona I, Custodio J, Barrero MJ, Peinado MA and Jordà M
Publicada:
1 jun 2020
Ahead of Print:
1 feb 2020
Resumen:
Alu repeats constitute a major fraction of human genome and for a small subset of them a role in gene regulation has been described. The number of studies focused on the functional characterization of particular Alu elements is very limited. Most Alu elements are DNA methylated and then assumed to lie in repressed chromatin domains. We hypothesize that Alu elements with low or variable DNA methylation are candidates for a functional role. In a genome-wide study in normal and cancer tissues, we pinpointed an Alu repeat (AluSq2) with differential methylation located upstream of the promoter region of the DIEXF gene. DIEXF encodes a highly conserved factor essential for the development of zebrafish digestive tract. To characterize the contribution of the Alu element to the regulation of DIEXF we analysed the epigenetic landscapes of the gene promoter and flanking regions in different cell types and cancers. Alternate epigenetic profiles (DNA methylation and histone modifications) of the AluSq2 element were associated with DIEXF transcript diversity as well as protein levels, while the epigenetic profile of the CpG island associated with the DIEXF promoter remained unchanged. These results suggest that AluSq2 might directly contribute to the regulation of DIEXF transcription and protein expression. Moreover, AluSq2 was DNA hypomethylated in different cancer types, pointing out its putative contribution to DIEXF alteration in cancer and its potential as tumoural biomarker.
Filiaciones:
:
Program of Predictive and Personalized Medicine of Cancer, Germans Trias i Pujol Research Institute (PMPPC-IGTP) , Barcelona, Spain
Pappa S:
Program of Predictive and Personalized Medicine of Cancer, Germans Trias i Pujol Research Institute (PMPPC-IGTP) , Barcelona, Spain
Díez-Villanueva A:
Program of Predictive and Personalized Medicine of Cancer, Germans Trias i Pujol Research Institute (PMPPC-IGTP) , Barcelona, Spain
Mallona I:
Program of Predictive and Personalized Medicine of Cancer, Germans Trias i Pujol Research Institute (PMPPC-IGTP) , Barcelona, Spain
Custodio J:
Program of Predictive and Personalized Medicine of Cancer, Germans Trias i Pujol Research Institute (PMPPC-IGTP) , Barcelona, Spain
Barrero MJ:
Center for Regenerative Medicine in Barcelona (CMRB), Avinguda de la Granvia de l'Hospitalet , Barcelona, Spain
:
Program of Predictive and Personalized Medicine of Cancer, Germans Trias i Pujol Research Institute (PMPPC-IGTP) , Barcelona, Spain
:
Program of Predictive and Personalized Medicine of Cancer, Germans Trias i Pujol Research Institute (PMPPC-IGTP) , Barcelona, Spain
Green Submitted, Green Published, Bronze
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