Allele-specific transcription factor binding in a cellular model of orofacial clefting.
Alleles
Binding Sites
Cell Line
Chromatin Immunoprecipitation Sequencing
Cleft Lip
/ genetics
Cleft Palate
/ genetics
Gene Expression Regulation, Developmental
Genetic Predisposition to Disease
Genome-Wide Association Study
Human Embryonic Stem Cells
/ metabolism
Humans
Mesenchymal Stem Cells
/ metabolism
Polymorphism, Single Nucleotide
Protein Binding
RNA-Seq
Transcription Factor AP-2
/ genetics
Transcriptome
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
02 02 2022
02 02 2022
Historique:
received:
03
08
2021
accepted:
17
01
2022
entrez:
3
2
2022
pubmed:
4
2
2022
medline:
11
3
2022
Statut:
epublish
Résumé
Non-syndromic cleft lip with/without cleft palate (nsCL/P) is a frequent congenital malformation with multifactorial etiology. While recent genome-wide association studies (GWAS) have identified several nsCL/P risk loci, the functional effects of the associated non-coding variants are largely unknown. Furthermore, additional risk loci remain undetected due to lack of power. As genetic variants might alter binding of transcription factors (TF), we here hypothesized that the integration of data from TF binding sites, expression analyses and nsCL/P GWAS might help to (i) identify functionally relevant variants at GWAS loci, and (ii) highlight novel risk variants that have been previously undetected. Analysing the craniofacial TF TFAP2A in human embryonic palatal mesenchyme (HEPM) cells, we identified 2845 TFAP2A ChIP-seq peaks, several of which were located near nsCL/P candidate genes (e.g. MSX1 and SPRY2). Comparison with independent data suggest that 802 of them might be specific to craniofacial development, and genes near these peaks are enriched in processes relevant to nsCL/P. Integration with nsCL/P GWAS data, however, did not show robust evidence for co-localization of common nsCL/P risk variants with TFAP2A ChIP-seq peaks. This data set represents a new resource for the analyses of craniofacial processes, and similar approaches with additional cell lines and TFs could be applied to generate further insights into nsCL/P etiology.
Identifiants
pubmed: 35110662
doi: 10.1038/s41598-022-05876-7
pii: 10.1038/s41598-022-05876-7
pmc: PMC8810875
doi:
Substances chimiques
TFAP2A protein, human
0
Transcription Factor AP-2
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1807Informations de copyright
© 2022. The Author(s).
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