As well as the adjuvant treatment of breast cancer active inhibitor of 17b-HSD1

Identified genes are involved in a wide range of cellular processes suggesting new and expanded roles for this transcription factor. As detailed above, Arx directly regulates genes required for R428 Axl inhibitor cell-cycle control, tight-junction dynamics, cell morphology, neuronal migration and differentiation as well as synaptic plasticity modulation, neurotransmission and axonal guidance. Among the different targets we identified, a number of genes are known to be important for brain development and some have already been linked to human disorders. But in addition, we identified new genes which may be good candidates to test in human neurological and psychological diseases. Further studies to understand their function and their relation to Arx will certainly bring new insight into the understanding of the pathophysiology of intellectual disability and epilepsy. Chromatin immunoprecipitation on embryonic brains from wild-type mice was performed following a similar protocol. All animal procedures were performed in accordance with French and international guidelines and were approved by the French review board ministe`re . Briefly, adult pregnant female mice were killed by cervical dislocation and brains were extracted from day 15.5 embryos in cold PBS. Following brain isolation, the whole forebrain including ventral telencephalon, thalamus, cerebral cortex and olfactory bulbs were frozen in liquid nitrogen and kept at 280uC for further experiments. For each experiment, tissue was pooled from 3 embryos. Tissue disaggregation and homogenization were performed in liquid nitrogen using a pestle and a mortar. Samples were then transferred into a 15 ml Falcon tube and fixed in a solution containing PBS, 1% formaldehyde and Protease Inhibitor Cocktail . Following steps were identical to those described above. Intensity data on each array were normalized with the Lowess method , pooled and represented on a graph. To identify regions of significant Arx association, the enrichment of each probe on the array was calculated as the log2-ratio of the intensities of Arx-immunoprecipitated DNA to control input chromatin . One first important assumption is that points corresponding to non positive probes are distributed symmetrically around the axis x= y.

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