Reference : Transcription impairment and cell migration defects in elongator-depleted cells: Impl...
Scientific journals : Article
Life sciences : Biochemistry, biophysics & molecular biology
http://hdl.handle.net/2268/2904
Transcription impairment and cell migration defects in elongator-depleted cells: Implication for familial dysautonomia
English
Close, Pierre mailto [Université de Liège - ULg > Département de pharmacie > Chimie médicale >]
Hawkes, Nicola [Cancer Research London Research Institute - UK > Clare Hall Laboratories > > >]
Cornez, Isabelle [Université de Liège - ULg > > Chimie médicale >]
Creppe, Catherine mailto [Université de Liège - ULg > > Chimie médicale >]
Lambert, Charles A [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Laboratoire des tissus conjonctifs >]
Rogister, Bernard mailto [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Biochimie et physiologie générales, et biochimie humaine >]
Siebenlist, Ulrich [National Institute of Health - Bethesda Mariland > National Inst. of Allergy and infectious disease > Laboratory of Immunoregulation > >]
Merville, Marie-Paule mailto [Université de Liège - ULg > Département de pharmacie > Chimie médicale >]
Slaugenhaupt, Susan A [Harvard Medical School > Massachusetts General Hospital > Center for Human Genetic Research > >]
Bours, Vincent mailto [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Génétique générale et humaine]
Svejstrup, Jesper Q [Cancer Research UK London Research Institute > Clare Hall laboratories > > >]
Chariot, Alain mailto [Université de Liège - ULg > Département de pharmacie > Chimie médicale >]
May-2006
Molecular Cell
Cell Press
22
4
521-531
Yes (verified by ORBi)
International
1097-2765
1097-4164
Cambridge
MA
[en] Transcription ; familial dysautonomia ; acetylation ; Carrier Proteins/antagonists & inhibitors/genetics/metabolism ; Cell Line ; Cell Movement/genetics/physiology ; Dysautonomia, Familial/etiology/genetics/metabolism/pathology ; Gene Expression Regulation ; Hela Cells ; Histones/metabolism ; Humans ; Mutation ; RNA Interference ; RNA Polymerase II/metabolism ; Transcription, Genetic
[en] Mutations in IKBKAP, encoding a subunit of Elongator, cause familial dysautonomia (FD), a severe neuro-developmental disease with complex clinical characteristics. Elongator was previously linked not only with transcriptional elongation and histone acetylation but also with other cellular processes. Here, we used RNA interference (RNAi) and fibroblasts from FD patients to identify Elongator target genes and study the role of Elongator in transcription. Strikingly, whereas Elongator is recruited to both target and nontarget genes, only target genes display histone H3 hypoacetylation and progressively lower RNAPII density through the coding region in FD cells. Interestingly, several target genes encode proteins implicated in cell motility. Indeed, characterization of IKAP/hELP1 RNAi cells, FD fibroblasts, and neuronal cell-derived cells uncovered defects in this cellular function upon Elongator depletion. These results indicate that defects in Elongator function affect transcriptional elongation of several genes and that the ensuing cell motility deficiencies may underlie the neuropathology of FD patients.
Researchers ; Professionals ; Students
http://hdl.handle.net/2268/2904
also: http://hdl.handle.net/2268/75225 ; http://hdl.handle.net/2268/84268
10.1016/j.molcel.2006.04.017

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