Overlapping DNA methylation dynamics in mouse intestinal cell differentiation and early stages of malignant progression.

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  • dc.contributor.author Forn, Martaca
  • dc.contributor.author Díez-Villanueva, Annaca
  • dc.contributor.author Merlos-Suárez, Annaca
  • dc.contributor.author Muñoz, Marca
  • dc.contributor.author Lois, Sergica
  • dc.contributor.author Carriò, Elviraca
  • dc.contributor.author Jordà, Mireiaca
  • dc.contributor.author Bigas Salvans, Annaca
  • dc.contributor.author Batlle Gómez, Eduardca
  • dc.contributor.author Peinado, Miguel A.ca
  • dc.date.accessioned 2015-05-26T09:55:50Z
  • dc.date.available 2015-05-26T09:55:50Z
  • dc.date.issued 2015
  • dc.description.abstract Mouse models of intestinal crypt cell differentiation and tumorigenesis have been used to characterize the molecular mechanisms underlying both processes. DNA methylation is a key epigenetic mark and plays an important role in cell identity and differentiation programs and cancer. To get insights into the dynamics of cell differentiation and malignant transformation we have compared the DNA methylation profiles along the mouse small intestine crypt and early stages of tumorigenesis. Genome-scale analysis of DNA methylation together with microarray gene expression have been applied to compare intestinal crypt stem cells (EphB2high), differentiated cells (EphB2negative), ApcMin/+ adenomas and the corresponding non-tumor adjacent tissue, together with small and large intestine samples and the colon cancer cell line CT26. Compared with late stages, small intestine crypt differentiation and early stages of tumorigenesis display few and relatively small changes in DNA methylation. Hypermethylated loci are largely shared by the two processes and affect the proximities of promoter and enhancer regions, with enrichment in genes associated with the intestinal stem cell signature and the PRC2 complex. The hypermethylation is progressive, with minute levels in differentiated cells, as compared with intestinal stem cells, and reaching full methylation in advanced stages. Hypomethylation shows different signatures in differentiation and cancer and is already present in the non-tumor tissue adjacent to the adenomas in ApcMin/+ mice, but at lower levels than advanced cancers. This study provides a reference framework to decipher the mechanisms driving mouse intestinal tumorigenesis and also the human counterpart.ca
  • dc.description.sponsorship MF and EC were supported by respective FPI fellowships from the Ministerio de Economía y Competitividad. AMS held an AECC postdoctoral fellowship. AD-V was supported in part by a contract PTC2011-1091 from Ministerio de Economía y Competitividad. This work was supported by grants from the Ministerio de Economía y Competitividad/n(SAF2011/23638) to MAP; and an ERC grant to EB.
  • dc.format.mimetype application/pdfca
  • dc.identifier.citation Forn M, Díez-Villanueva A, Merlos-Suárez A, Muñoz M, Lois S, Carriò E. et al. Overlapping DNA methylation dynamics in mouse intestinal cell differentiation and early stages of malignant progression. PLoS One. 2015 May 1;10(5):e0123263. doi: 10.1371/journal.pone.0123263. eCollection 2015.ca
  • dc.identifier.doi http://dx.doi.org/ 10.1371/journal.pone.0123263
  • dc.identifier.issn 1932-6203
  • dc.identifier.uri http://hdl.handle.net/10230/23652
  • dc.language.iso engca
  • dc.publisher Public Library of Scienceca
  • dc.relation.ispartof PLoS One. 2015 May 1;10(5):e0123263
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/SAF2011-23638
  • dc.rights © 2015 Forn et al. This is an openaccess article distributed under the terms of the http://creativecommons.org/licenses/by/4.0/, which permits unrestricted use, distribution, and reproduction in anymedium, provided the original author and source arecredited.ca
  • dc.rights.accessRights info:eu-repo/semantics/openAccessca
  • dc.rights.uri http://creativecommons.org/licenses/by/4.0/ca
  • dc.subject.other Intestins -- Càncerca
  • dc.title Overlapping DNA methylation dynamics in mouse intestinal cell differentiation and early stages of malignant progression.ca
  • dc.type info:eu-repo/semantics/articleca
  • dc.type.version info:eu-repo/semantics/publishedVersionca

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