mir152 hypomethylation as a mechanism for non-syndromic cleft lip and palate

Autor(es)

Alvizi, Lucas ; Brito, Luciano Abreu ; Kobayashi, Gerson Shigeru ; Bischain, Barbara ; Fernandes da Silva, Camila Bassi ; Guimaraes Ramos, Sofia Ligia ; Wang, Jaqueline ; Passos-Bueno, Maria Rita

• Tipo de documento: Artigo Científico
• Fonte: Epigenetics; v. 17, n. 13, p. 18-pg., 2022-09-01.

Resumo

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. (AU)

• Processo FAPESP: 13/08028-1 - CEGH-CEL - Centro de Estudos do Genoma Humano e de Células-Tronco
• Beneficiário: Mayana Zatz
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
• Processo FAPESP: 16/23648-4 - Investigação da relevância etiológica de novos genes candidatos às fissuras orofaciais
• Beneficiário: Luciano Abreu Brito
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado