Alvizi, L;
Brito, LA;
Kobayashi, GS;
Bischain, B;
da Silva, CBF;
Ramos, SLG;
Wang, J;
(2022)
mir152 hypomethylation as a mechanism for non-syndromic cleft lip and palate.
Epigenetics
, 17
(13)
pp. 2278-2295.
10.1080/15592294.2022.2115606.
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Abstract
Non-syndromic cleft lip with or without cleft palate (NSCLP), the most common human craniofacial malformation, is a complex disorder given its genetic heterogeneity and multifactorial component revealed by genetic, epidemiological, and epigenetic findings. Epigenetic variations associated with NSCLP have been identified; however, functional investigation has been limited. Here, we combined a reanalysis of NSCLP methylome data with genetic analysis and used both in vitro and in vivo approaches to dissect the functional effects of epigenetic changes. We found a region in mir152 that is frequently hypomethylated in NSCLP cohorts (21–26%), leading to mir152 overexpression. mir152 overexpression in human neural crest cells led to downregulation of spliceosomal, ribosomal, and adherens junction genes. In vivo analysis using zebrafish embryos revealed that mir152 upregulation leads to craniofacial cartilage impairment. Also, we suggest that zebrafish embryonic hypoxia leads to mir152 upregulation combined with mir152 hypomethylation and also analogous palatal alterations. We therefore propose that mir152 hypomethylation, potentially induced by hypoxia in early development, is a novel and frequent predisposing factor to NSCLP.
| Type: | Article |
|---|---|
| Title: | mir152 hypomethylation as a mechanism for non-syndromic cleft lip and palate |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1080/15592294.2022.2115606 |
| Publisher version: | https://doi.org/10.1080/15592294.2022.2115606 |
| Language: | English |
| Additional information: | © 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
| Keywords: | Epigenetics, cleft lip/palate, craniofacial marformation, microRNA, Animals, Humans, Cleft Lip, Cleft Palate, Zebrafish, Genetic Predisposition to Disease, DNA Methylation, Hypoxia, Polymorphism, Single Nucleotide, MicroRNAs |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Cell and Developmental Biology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10166037 |
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