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| Status |
Public on Dec 22, 2011 |
| Title |
Comparison of gene expression between Arx-transfected N2a cells and cells transfected by the corresponding empty vector |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Genetic investigations of X-linked intellectual disabilities have implicated the ARX (Aristaless-related homeobox) gene in a wide spectrum of disorders extending from phenotypes characterised by severe neuronal migration defects such as lissencephaly, to mild or moderate forms of mental retardation without apparent brain abnormalities but with associated features of dystonia and epilepsy. Analysis of Arx spatio-temporal localisation profile in mouse revealed expression in telencephalic structures, mainly restricted to populations of GABAergic neurons at all stages of development. Furthermore, studies of the effects of ARX loss of function in humans and animal models revealed varying defects, suggesting multiple roles of this gene during brain development. However, to date, little is known about how ARX functions as a transcription factor and the nature of its targets. To better understand its role, we combined chromatin immunoprecipitation and mRNA expression with microarray analysis and identified a total of 1006 gene promoters bound by Arx in transfected neuroblastoma (N2a) cells and in mouse embryonic brain. Some of these promoters were enriched for a sequence very similar to a motif previously identified as Arx-binding motif and approximately 24% of Arx-bound genes were found to show expression changes following Arx overexpression or knock-down. Several of the Arx target genes we identified are known to be important for a variety of functions in brain development, including axonal guidance and synaptic plasticity and some of them suggest new functions for Arx. Overall, these results identified multiple new candidate targets for Arx and should help to better understand the pathophysiological mechanisms of intellectual disability and epilepsy associated with ARX mutations.
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| Overall design |
N2a cells were transfected with either Arx or the corresponding empty vector. Eight different independent experiments were performed. The 16 samples were randomly distributes on the 2 expression microarrays.
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| Contributor(s) |
Quillé M, Hirchaud E, Carat S, Baron D, Houlgatte R, Friocourt G |
| Citation(s) |
21966449 |
| |
| Submission date |
Jun 24, 2011 |
| Last update date |
Jan 19, 2018 |
| Contact name |
Gaelle Friocourt |
| E-mail(s) |
gaellefriocourt@yahoo.fr
|
| Phone |
+33 298443895
|
| Fax |
+33 298467910
|
| Organization name |
Inserm U613
|
| Department |
Molecular Genetics
|
| Street address |
46 rue Félix Le Dantec, CS51819
|
| City |
Brest |
| ZIP/Postal code |
29218 |
| Country |
France |
| |
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| Platforms (1) |
| GPL10333 |
Agilent-026655 Whole Mouse Genome Microarray 4x44K v2 (Feature Number version) |
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| Samples (16)
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| This SubSeries is part of SuperSeries: |
| GSE30191 |
ARX transcription factor implicated in mental retardation and epilepsy |
|
| Relations |
| BioProject |
PRJNA155105 |
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