PUBLICATION
A TAF11 variant contributes to non-syndromic cleft lip only through modulating neural crest cell migration
- Authors
- Li, D., Tian, Y., Vona, B., Yu, X., Lin, J., Ma, L., Lou, S., Li, X., Zhu, G., Wang, Y., Du, M., Wang, L., Pan, Y.
- ID
- ZDB-PUB-250109-70
- Date
- 2024
- Source
- Human molecular genetics : (Journal)
- Registered Authors
- Keywords
- TAF11; craniofacial development, cranial neural crest cells migration, transcription regulation
- MeSH Terms
-
- Mutation
- TATA-Binding Protein Associated Factors*/genetics
- TATA-Binding Protein Associated Factors*/metabolism
- Transcription Factor TFIID/genetics
- Transcription Factor TFIID/metabolism
- Animals
- Humans
- Zebrafish*/genetics
- Neural Crest*/metabolism
- Neural Crest*/pathology
- Cleft Lip*/genetics
- Cleft Lip*/metabolism
- Cleft Lip*/pathology
- Pedigree*
- Female
- Male
- Cell Movement*/genetics
- PubMed
- 39727181 Full text @ Hum. Mol. Genet.
Citation
Li, D., Tian, Y., Vona, B., Yu, X., Lin, J., Ma, L., Lou, S., Li, X., Zhu, G., Wang, Y., Du, M., Wang, L., Pan, Y. (2024) A TAF11 variant contributes to non-syndromic cleft lip only through modulating neural crest cell migration. Human molecular genetics. :.
Abstract
The NC_000006.12: g.34887814C>G variant in TAF11 was identified as a potential functional variant in a Chinese pedigree including two non-syndromic cleft lip only (NSCLO) cases. Applying Chromatin Immunoprecipitation (ChIP), Electrophoretic mobility shift and super-shift assays, we found that the mutant G allele recruited more STAT1 and STAT3, and increased the expression of TAF11. RNA sequencing, GO and KEGG pathway enrichment, ChIP and dual-luciferase reporter assays revealed that TAF11 downregulated CDH1 and CTNND1 in the cell adhesion pathway by binding to their promoter regions and inhibiting transcriptional activities. Alcian blue staining, time-lapse photography, whole-mount in situ hybridization, phospho-Histone H3 immunofluorescence and TUNEL assays indicated that TAF11 and taf11 overexpression (TAF11OE and taf11OE, respectively) contributed to disturbed migration of cranial neural crest cells and abnormal craniofacial development, as well as increased death and deformity rates in zebrafish. In conclusion, a functionally relevant TAF11 variant, affecting cell migration via modulating CDH1 and CTNND1, was associated with etiology of NSCLO.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping