2026-06-16T14:02:00Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/78282024-11-29T16:24:34Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597

00925njm 22002777a 4500 dc Torres-Ruiz Raul, Raúl author Benítez-Burraco, Antonio author Martínez-Lage, Marta author Rodriguez Perales, Sandra author García-Bellido, Paloma author 2019-05-02 BACKGROUND: Mutations in the coding region of FOXP2 are known to cause speech and language impairment. However, it is not clear how dysregulation of the gene contributes to language deficit. Interestingly, microdeletions of the region downstream the gene have been associated with cognitive deficits. METHODS: Here, we investigate changes in FOXP2 expression in the SK-N-MC neuroblastoma human cell line after deletion by CRISPR-Cas9 of two enhancers located downstream of the gene. RESULTS: Deletion of any of these two functional enhancers downregulates FOXP2, but also upregulates the closest 3' gene MDFIC. Because this effect is not statistically significant in a HEK 293 cell line, derived from the human kidney, both enhancers might confer a tissue specific regulation to both genes. We have also found that the deletion of any of these enhancers downregulates six well-known FOXP2 target genes in the SK-N-MC cell line. CONCLUSIONS: We expect these findings contribute to a deeper understanding of how FOXP2 and MDFIC are regulated to pace neuronal development supporting cognition, speech and language. BMC Med Genet. 2019;20(1):65. 10.1186/s12881-019-0810-2 1471-2350 1471-2350 BMC medical genetics 31046704 http://hdl.handle.net/20.500.12105/7828 CRISPR-genome editing Chromosomal rearrangement FOXP2 Functional enhancers MDFIC Spanish Speech and language impairment Functional characterization of two enhancers located downstream FOXP2