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PXD008084

DataSet Summary

  • HostingRepository: PRIDE
  • AnnounceDate: 2018-04-16
  • AnnouncementXML: Submission_2018-04-16_01:49:31.xml
  • DigitalObjectIdentifier:
  • ReviewLevel: Peer-reviewed dataset
  • DatasetOrigin: Original data
  • RepositorySupport: Unsupported dataset by repository
  • PrimarySubmitter: Farrah El-Saafin
  • Title: TAF8 MUTATION CAUSES INTELLECUAL DISABILITY, TFIID DISASSEMBLY WITH NO EFFECT ON RNA POLYMERASE II TRANSCRIPTION
  • Description: The human general transcription factor TFIID is composed of the TATA-binding protein (TBP) and 13 TBP-associated factors (TAFs). In eukaryotic cells, TFIID nucleates RNA Polymerase II (Pol II) preinitiation complex formation on gene promoters and thus, is crucial for Pol II transcription. Germline knock out of several mouse TFIID subunits (Tbp, Taf7, Taf8, and Taf10) results in lethality at embryonic day 4.0, demonstrating the fundamental role of holo-TFIID in transcription. We identified a child harboring a splice-site mutation in TAF8, who has intellectual disability, poor growth, progressive spasticity and microcephaly. The c.781-G>A TAF8 mutation in this patient resulted in a frame shift, which affected the final 50 carboxy terminal amino acids of TAF8. We found that the mutant TAF8 protein is unstable and the patient c.781-G>A TAF8 primary fibroblasts did not form canonical TFIID complexes. Astonishingly however, genome-wide RNA pol II occupancy and pre-mRNA transcription on the tested genes was unaffected in the patient’s primary fibroblasts. This study indicates that perturbed TFIID function is less deleterious for transcription in human cells than originally anticipated.
  • SpeciesList: scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
  • ModificationList: iodoacetic acid derivatized residue; deamidated residue
  • Instrument: LTQ Orbitrap Elite

Dataset History

VersionDatetimeStatusChangeLog Entry
02017-10-31 02:37:44ID requested
12018-04-16 01:49:33announced

Publication List

  1. El-Saafin F, Curry C, Ye T, Garnier JM, Kolb-Cheynel I, Stierle M, Downer NL, Dixon MP, Negroni L, Berger I, Thomas T, Voss AK, Dobyns W, Devys D, Tora L, Homozygous TAF8 mutation in a patient with intellectual disability results in undetectable TAF8 protein, but preserved RNA polymerase II transcription. Hum Mol Genet, 27(12):2171-2186(2018) [pubmed]

Keyword List

  1. curator keyword: Biomedical
  2. submitter keyword: Patient, intellectual disability, TFIID, TATA binding protein (TBP), TBP-associated factor (TAF), RNA polymerase II (Pol II), splice site mutation, frame shift, chromatin immunoprecipitation (ChIP)

Contact List

    Laszlo Tora
    • contact affiliation: Institut de Génétique et de Biologie Moléculaire et Cellulaire IGBMC, Illkirch, France
 Centre National de la Recherche Scientifique, UMR7104, Illkirch, France
 Institut National de la Santé et de la Recherche Médicale, U964, Illkirch, France
 Université de Strasbourg, Illkirch, France
    • contact email: laszlo@igbmc.fr
    • lab head:
    Farrah El-Saafin
    • contact affiliation: IGBMC
    • contact email: elsaafif@igbmc.fr
    • dataset submitter:

Full Dataset Link List

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  2. PRIDE project URI
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