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Title: Overexpression of DNMT3b target genes during Enteric Nervous System development contribute to the onset of Hirschsprung disease.
Authors: Villalba-Benito, Leticia
Torroglosa, Ana
Fernández, Raquel María
Ruíz-Ferrer, Macarena
Moya-Jiménez, María José
Antiñolo, Guillermo
Borrego, Salud
metadata.dc.subject.mesh: Age of Onset
Case-Control Studies
Child, Preschool
DNA (Cytosine-5-)-Methyltransferases
DNA Methylation
Enteric Nervous System
Gene Expression Regulation
High-Throughput Nucleotide Sequencing
Hirschsprung Disease
Neural Crest
Issue Date: 24-Jul-2017
Abstract: Hirschsprung disease (HSCR) is attributed to a failure of neural crest cells (NCCs) to migrate, proliferate, differentiate and/or survive in the bowel wall during embryonic Enteric Nervous System (ENS) development. ENS formation is the result from a specific gene expression pattern regulated by epigenetic events, such DNA methylation by the DNA methyltransferases (DNMTs), among other mechanisms. Specifically, DNMT3b de novo methyltransferase is associated with NCCs development and has been shown to be implicated in ENS formation and in HSCR. Aiming to elucidate the specific mechanism underlying the DNMT3b role in such processes, we have performed a chromatin immunoprecipitation coupled with massively parallel sequencing analysis to identify the DNMT3B target genes in enteric precursor cells (EPCs) from mice. Moreover, the expression patterns of those target genes have been analyzed in human EPCs from HSCR patients in comparison with controls. Additionally, we have carried out a search of rare variants in those genes in a HSCR series. Through this approach we found 9 genes showing a significantly different expression level in both groups. Therefore, those genes may have a role in the proper human ENS formation and a failure in their expression pattern might contribute to this pathology.
metadata.dc.identifier.doi: 10.1038/s41598-017-06539-8
Appears in Collections:Producción 2020

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