Transcription impairment and cell migration defects in elongator-depleted cells: implication for familial dysautonomia.
Mol Cell
; 22(4): 521-31, 2006 May 19.
Article
em En
| MEDLINE
| ID: mdl-16713582
ABSTRACT
Mutations in IKBKAP, encoding a subunit of Elongator, cause familial dysautonomia (FD), a severe neurodevelopmental 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.
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Base de dados:
MEDLINE
Assunto principal:
Proteínas de Transporte
/
Disautonomia Familiar
Limite:
Humans
Idioma:
En
Ano de publicação:
2006
Tipo de documento:
Article