Involvement of DNMT3B in the pathogenesis of Hirschsprung disease and its possible role as a regulator of neurogenesis in the human enteric nervous system

Torroglosa, Ana; Enguix-Riego, María Valle; Fernández, Raquel M.; Roman-Rodriguez, Francisco J; Moya-Jiménez, María José; Agustín, Juan Carlos de; Antiñolo, Guillermo; Borrego, Salud

doi:10.1038/gim.2014.17

Cited by 29 publications

(30 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is worthy to note that all the genes observed to be differentially expressed in HSCR patients versus controls are up-regulated in the first group, which fits with the lower global DNA methylation due to the decreased expression of DNMT3b described in HSCR patients 7 . In addition, we carried out a search of rare variants in those genes in a HSCR series.…”

Section: Discussionsupporting

confidence: 70%

“…In this sense, the de novo methyltransferase DNMT3b has been associated with HSCR 7 and, therefore, we have focused in the identification of DNMT3b target genes to elucidate the pathways and genes which are regulated by this methyltranferase. Taking into account that in the context of rare disorders such as HSCR the recruitment of a high number of patients is really difficult, we designed an indirect experiment in EPCs from mouse to identify the possible Dnmt3b target genes by ChIP-seq, since with this kind of samples we have no limitations regarding the minimal starting quantity required for the assays.…”

Section: Discussionmentioning

confidence: 99%

“…Epigenetic mechanisms are acquiring increasing evidence of playing a major role in the onset of HSCR 7, 8 . Different epigenetic mechanisms are known, such as DNA methylation by the DNA methyltransferases (DNMT1, DNMT3a and DNMT3b).…”

Section: Introductionmentioning

confidence: 99%

“…DNMT3b has been described as the methyltransferase that regulates the initial steps of progenitor cell differentiation during embryogenesis 12 . In addition, it has been shown that the expression of DNMT3b is lower in EPCs from HSCR patients compared with controls and this aberrant expression leads to a decrease of the global DNA methylation 7 , which may be contributing to an inappropriate gene expression pattern and to the onset of this pathology.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Overexpression of DNMT3b target genes during Enteric Nervous System development contribute to the onset of Hirschsprung disease

Villalba‐Benito

Torroglosa

Fernández

et al. 2017

Sci Rep

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionsupporting

confidence: 70%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Overexpression of DNMT3b target genes during Enteric Nervous System development contribute to the onset of Hirschsprung disease

Villalba‐Benito

Torroglosa

Fernández

et al. 2017

Sci Rep

Self Cite

View full text Add to dashboard Cite

show abstract

“…Recently, it has been described to play a role in the development of the ENS and in the onset of HSCR disease (Torroglosa et al, 2014). A decreased expression of DNMT3B was observed in enteric precursors isolated from HSCR patients, as a result of DNA hypomethylation in patients versus controls.…”

Section: Dnmt3bmentioning

confidence: 99%

Epigenetics in ENS development and Hirschsprung disease

Torroglosa

Alves

Fernández

et al. 2016

Developmental Biology

View full text Add to dashboard Cite

Hirschsprung disease (HSCR, OMIM 142623) is a neurocristopathy caused by a failure of the enteric nervous system (ENS) progenitors derived from neural crest cells (NCCs), to migrate, proliferate, differentiate or survive to and within the gastrointestinal tract, resulting in aganglionosis in the distal colon. The formation of the ENS is a complex process, which is regulated by a large range of molecules and signalling pathways involving both the NCCs and the intestinal environment. This tightly regulated process needs correct regulation of the expression of ENS specific genes. Alterations in the expression of these genes can have dramatic consequences. Several mechanisms that control the expression of genes have been described, such as DNA modification (epigenetic mechanisms), regulation of transcription (transcription factor, enhancers, repressors and silencers), post-transcriptional regulation (3'UTR and miRNAs) and regulation of translation. In this review, we focus on the epigenetic DNA modifications that have been described so far in the context of the ENS development. Moreover we describe the changes that are found in relation to the onset of HSCR.

show abstract

Nucleic acid methylation and orofacial morphogenesis

Seelan

Pisano

Greene

2019

Birth Defects Research

View full text Add to dashboard Cite

In this review, we highlight the current state of knowledge of the diverse roles nucleic acid methylation plays in the embryonic development of the orofacial region and how aberrant methylation may contribute to orofacial clefts. We also consider the role of methylation in the regulation of neural crest cell function as it pertains to orofacial ontogeny. Changes in DNA methylation, as a consequence of environmental effects, have been observed in the regulatory regions of several genes, potentially identifying new candidate genes for orofacial clefting and opening promising new avenues for further research. While the focus of this review is primarily on the nonsyndromic forms of orofacial clefting, syndromic forms are briefly discussed in the context of aberrant nucleic acid methylation. K E Y W O R D Sbirth defects, epigenetics, neural crest cells, nucleic acid methylation, orofacial clefts

show abstract

Involvement of DNMT3B in the pathogenesis of Hirschsprung disease and its possible role as a regulator of neurogenesis in the human enteric nervous system

Cited by 29 publications

References 36 publications

Overexpression of DNMT3b target genes during Enteric Nervous System development contribute to the onset of Hirschsprung disease

Overexpression of DNMT3b target genes during Enteric Nervous System development contribute to the onset of Hirschsprung disease

Epigenetics in ENS development and Hirschsprung disease

Nucleic acid methylation and orofacial morphogenesis

Contact Info

Product

Resources

About