PUBLICATION
mir152 hypomethylation as a mechanism for non-syndromic cleft lip and palate
- Authors
- Alvizi, L., Brito, L.A., Kobayashi, G.S., Bischain, B., da Silva, C.B.F., Ramos, S.L.G., Wang, J., Passos-Bueno, M.R.
- ID
- ZDB-PUB-220902-5
- Date
- 2022
- Source
- Epigenetics 17(13): 2278-2295 (Journal)
- Registered Authors
- Keywords
- Epigenetics, cleft lip/palate, craniofacial marformation, microRNA
- MeSH Terms
-
- Animals
- Cleft Lip*/genetics
- Cleft Palate*/genetics
- DNA Methylation
- Genetic Predisposition to Disease
- Humans
- Hypoxia/genetics
- MicroRNAs*/genetics
- Polymorphism, Single Nucleotide
- Zebrafish/genetics
- PubMed
- 36047706 Full text @ Epigenetics
Citation
Alvizi, L., Brito, L.A., Kobayashi, G.S., Bischain, B., da Silva, C.B.F., Ramos, S.L.G., Wang, J., Passos-Bueno, M.R. (2022) mir152 hypomethylation as a mechanism for non-syndromic cleft lip and palate. Epigenetics. 17(13):2278-2295.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping