RT Journal Article
T1 Overexpression of DNMT3b target genes during Enteric Nervous System development contribute to the onset of Hirschsprung disease.
A1 Villalba-Benito, Leticia
A1 Torroglosa, Ana
A1 Fernandez, Raquel Maria
A1 Ruiz-Ferrer, Macarena
A1 Moya-Jimenez, Maria Jose
A1 Antiñolo, Guillermo
A1 Borrego, Salud
K1 Age of Onset
K1 Case-Control Studies
K1 Enteric Nervous System
K1 Gene Expression Regulation
K1 Infant
K1 Neural Crest
AB 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.
PB Nature Publishing Group
YR 2017
FD 2017-07-24
LK http://hdl.handle.net/10668/11433
UL http://hdl.handle.net/10668/11433
LA en
DS RISalud
RD Apr 18, 2025