ZFIN ID: ZDB-PUB-190726-3
TAF1, associated with intellectual disability in humans, is essential for embryogenesis and regulates neurodevelopmental processes in zebrafish
Gudmundsson, S., Wilbe, M., Filipek-Górniok, B., Molin, A.M., Ekvall, S., Johansson, J., Allalou, A., Gylje, H., Kalscheuer, V.M., Ledin, J., Annerén, G., Bondeson, M.L.
Date: 2019
Source: Scientific Reports   9: 10730 (Journal)
Registered Authors: Filipek-Górniok, Beata, Ledin, Johan
Keywords: none
MeSH Terms:
  • Adolescent
  • Adult
  • Animals
  • Child
  • Child, Preschool
  • Female
  • Gene Expression Profiling
  • Gene Knockdown Techniques
  • Histone Acetyltransferases/genetics
  • Histone Acetyltransferases/physiology*
  • Humans
  • Intellectual Disability/genetics*
  • Male
  • Mental Retardation, X-Linked/genetics
  • Nervous System/embryology
  • Nervous System/growth & development*
  • Pedigree
  • TATA-Binding Protein Associated Factors/genetics
  • TATA-Binding Protein Associated Factors/physiology*
  • Transcription Factor TFIID/genetics
  • Transcription Factor TFIID/physiology*
  • Zebrafish/embryology
  • Zebrafish/growth & development*
  • Zebrafish Proteins/physiology*
PubMed: 31341187 Full text @ Sci. Rep.
The TATA-box binding protein associated factor 1 (TAF1) protein is a key unit of the transcription factor II D complex that serves a vital function during transcription initiation. Variants of TAF1 have been associated with neurodevelopmental disorders, but TAF1's molecular functions remain elusive. In this study, we present a five-generation family affected with X-linked intellectual disability that co-segregated with a TAF1 c.3568C>T, p.(Arg1190Cys) variant. All affected males presented with intellectual disability and dysmorphic features, while heterozygous females were asymptomatic and had completely skewed X-chromosome inactivation. We investigated the role of TAF1 and its association to neurodevelopment by creating the first complete knockout model of the TAF1 orthologue in zebrafish. A crucial function of human TAF1 during embryogenesis can be inferred from the model, demonstrating that intact taf1 is essential for embryonic development. Transcriptome analysis of taf1 zebrafish knockout revealed enrichment for genes associated with neurodevelopmental processes. In conclusion, we propose that functional TAF1 is essential for embryonic development and specifically neurodevelopmental processes.