A TAF11 variant contributes to non-syndromic cleft lip only through modulating neural crest cell migration

Dandan Li; Yu Tian; Barbara Vona; Xin Yu; Junyan Lin; Lan Ma; Shu Lou; Xiaofeng Li; Guirong Zhu; Yuting Wang; Mulong Du; Lin Wang; Yongchu Pan

doi:10.1093/hmg/ddae188

A TAF11 variant contributes to non-syndromic cleft lip only through modulating neural crest cell migration

Hum Mol Genet. 2024 Dec 27:ddae188. doi: 10.1093/hmg/ddae188. Online ahead of print.

Authors

Dandan Li^{1

2

3}, Yu Tian⁴, Barbara Vona^{5

6}, Xin Yu⁷, Junyan Lin^{1

2

3}, Lan Ma^{2

3}, Shu Lou^{1

2

3}, Xiaofeng Li^{1

2

3}, Guirong Zhu^{2

3}, Yuting Wang^{2

3}, Mulong Du^{8

9}, Lin Wang^{1

2

3}, Yongchu Pan^{1

2

3}

Affiliations

¹ Department of Orthodontics, The Affiliated Stomatological Hospital of Nanjing Medical University, No. 1 Shanghai Road, Gulou District, Nanjing 210029, China.
² State Key Laboratory Cultivation Base of Research, Prevention and Treatment for Oral Diseases, Nanjing Medical University, No. 136 Hanzhong Road, Gulou District, Nanjing 210029, China.
³ Jiangsu Province Engineering Research Center of Stomatological Translational Medicine, Nanjing Medical University, No. 136 Hanzhong Road, Gulou District, Nanjing 210029, China.
⁴ Department of Stomatology, Zhenjiang First People's Hospital, People's Hospital Affiliated to Jiangsu University, No. 8 Electric Road, Runzhou District, Zhenjiang 212000, China.
⁵ Institute of Human Genetics, University Medical Center Göttingen, Robert-Koch-Str. 40, Göttingen 37075, Germany.
⁶ Institute for Auditory Neuroscience and Inner Ear Lab, University Medical Center Göttingen, Robert-Koch-Str. 40, Göttingen 37075, Germany.
⁷ Department of Orthodontics, Affiliated Nantong Stomatological Hospital of Nantong University, No. 36 Yuelong South Road, Chongchuan District, Nantong 226006, China.
⁸ Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, No. 101 Longmian Avenue, Jiangning District, Nanjing 211166, China.
⁹ Department of Biostatistics, Center for Global Health, School of Public Health, Nanjing Medical University, No. 101 Longmian Avenue, Jiangning District, Nanjing 211166, China.

PMID: 39727181
DOI: 10.1093/hmg/ddae188

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.

Keywords: TAF11; craniofacial development; cranial neural crest cells migration; transcription regulation.

Abstract

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