Defective transcription of ATF3 responsive genes, a marker for Cockayne Syndrome.
Activating Transcription Factor 3
/ genetics
Cell Cycle Proteins
Cell Line
Cockayne Syndrome
/ diagnosis
DNA Damage
DNA Helicases
/ genetics
DNA Repair Enzymes
/ genetics
Gene Expression Profiling
Genes, Immediate-Early
/ genetics
Genetic Markers
Humans
Mutation
Nerve Tissue Proteins
Neuregulin-1
Poly-ADP-Ribose Binding Proteins
/ genetics
RNA Polymerase II
/ metabolism
Transcription Factors
/ genetics
Transcription, Genetic
/ genetics
Ultraviolet Rays
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
24 01 2020
24 01 2020
Historique:
received:
26
04
2019
accepted:
07
01
2020
entrez:
26
1
2020
pubmed:
26
1
2020
medline:
15
12
2020
Statut:
epublish
Résumé
Cockayne syndrome (CS) is a rare genetic disorder caused by mutations (dysfunction) in CSA and CSB. CS patients exhibit mild photosensitivity and severe neurological problems. Currently, CS diagnosis is based on the inefficiency of CS cells to recover RNA synthesis upon genotoxic (UV) stress. Indeed, upon genotoxic stress, ATF3, an immediate early gene is activated to repress up to 5000 genes encompassing its responsive element for a short period of time. On the contrary in CS cells, CSA and CSB dysfunction impairs the degradation of the chromatin-bound ATF3, leading to a permanent transcriptional arrest as observed by immunofluorescence and ChIP followed by RT-PCR. We analysed ChIP-seq of Pol II and ATF3 promoter occupation analysis and RNA sequencing-based gene expression profiling in CS cells, as well as performed immunofluorescence study of ATF3 protein stability and quantitative RT-PCR screening in 64 patient cell lines. We show that the analysis of few amount (as for example CDK5RAP2, NIPBL and NRG1) of ATF3 dependent genes, could serve as prominent molecular markers to discriminate between CS and non-CS patient's cells. Such assay can significantly simplify the timing and the complexity of the CS diagnostic procedure in comparison to the currently available methods.
Identifiants
pubmed: 31980658
doi: 10.1038/s41598-020-57999-4
pii: 10.1038/s41598-020-57999-4
pmc: PMC6981198
doi:
Substances chimiques
ATF3 protein, human
0
Activating Transcription Factor 3
0
CDK5RAP2 protein, human
0
Cell Cycle Proteins
0
ERCC8 protein, human
0
Genetic Markers
0
NIPBL protein, human
0
NRG1 protein, human
0
Nerve Tissue Proteins
0
Neuregulin-1
0
Poly-ADP-Ribose Binding Proteins
0
Transcription Factors
0
RNA Polymerase II
EC 2.7.7.-
DNA Helicases
EC 3.6.4.-
ERCC6 protein, human
EC 3.6.4.12
DNA Repair Enzymes
EC 6.5.1.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1105Commentaires et corrections
Type : CommentIn
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