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Series GSE8547

Query DataSets for GSE8547

Status

Public on Dec 31, 2007

Title

Transcriptional targets of FOXP2 in human brain and lung

Organism

Homo sapiens

Experiment type

Genome binding/occupancy profiling by genome tiling array

Summary

Mutations in FOXP2, a member of the forkhead family of transcription factors, are the only known cause of developmental speech and language disorders in humans. To date, there are no known targets of human FOXP2 in the nervous system. The identification of FOXP2 targets in the developing human brain therefore provides a unique tool with which to explore the development of human language and speech. Here we define FOXP2 targets in human basal ganglia (BG) and inferior frontal cortex (IFC) utilizing chromatin immunoprecipitation followed by microarray analysis (ChIP-chip) and validate the functional regulation of targets in vitro. ChIP-chip identified 285 FOXP2 targets in fetal human brain; significant overlap of targets in BG and IFC, indicate a core set of 34 transcriptional targets of FOXP2. We identified targets specific to the IFC or BG, not observed in lung, suggesting important regional and tissue differences in FOXP2 activity. Many target genes are known to play critical roles in specific aspects of CNS patterning or development, such as neurite outgrowth, as well as plasticity. Subsets of the FOXP2 transcriptional targets are either under positive selection in humans, or differentially expressed between human and chimpanzee brain. This is the first ChIP-chip study using human brain tissue, making the FOXP2 target genes identified in these studies important to understanding the pathways regulating speech and language in the developing human brain. These data provide the first insight into the functional network of genes directly regulated by FOXP2 in human brain and by evolutionary comparisons, highlight genes likely to be involved in the development of human higher order cognitive processes.
Keywords: ChIP-chip

Overall design

Three independent brain samples were used for both the basal ganglia and inferior frontal cortex experiments. Two different pieces from the same lung tissue were used.

Contributor(s)

Spiteri E, Konopka G, Coppola G, Bomar J, Vernes S, Ou J, Fisher S, Ren B, Geschwind D

Citation(s)

17999357

Submission date

Jul 22, 2007

Last update date

Jan 17, 2013

Contact name

Daniel H Geschwind

E-mail(s)

[email protected]