PXD008084

PXD008084 is an original dataset announced via ProteomeXchange.

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.
HostingRepository	PRIDE
AnnounceDate	2018-04-16
AnnouncementXML	Submission_2018-04-16_01:49:31.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Farrah El-Saafin
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	iodoacetic acid derivatized residue; deamidated residue
Instrument	LTQ Orbitrap Elite

Revision	Datetime	Status	ChangeLog Entry
0	2017-10-31 02:37:44	ID requested
⏵ 1	2018-04-16 01:49:33	announced

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]

curator keyword: Biomedical

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)

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

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2018/04/PXD008084

PRIDE project URI

• PRIDE
  1. PXD008084
     1. Label: PRIDE project
     2. Name: TAF8 MUTATION CAUSES INTELLECUAL DISABILITY, TFIID DISASSEMBLY WITH NO EFFECT ON RNA POLYMERASE II TRANSCRIPTION