Multiple enhancers located in a 1-Mb region upstream of POU3F4 promote expression during inner ear development and may be required for hearing

Naranjo, Silvia; Voesenek, Krysta; Calle Mustienes, Elisa de la; Robert Moreno, Alexandre; Kokotas, Haris; Grigoriadou, Maria; Economides, John; Van Camp, Guy; Hilgert, Nele; Moreno, Felipe; Alsina i Español, Berta; Petersen, Michael B.; Kremer, Hannie; Gómez Skarmeta, José Luis

Multiple enhancers located in a 1-Mb region upstream of POU3F4 promote expression during inner ear development and may be required for hearing

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dc.contributor.author Naranjo, Silviaca
dc.contributor.author Voesenek, Krystaca
dc.contributor.author Calle Mustienes, Elisa de laca
dc.contributor.author Robert Moreno, Alexandreca
dc.contributor.author Kokotas, Harisca
dc.contributor.author Grigoriadou, Mariaca
dc.contributor.author Economides, Johnca
dc.contributor.author Van Camp, Guyca
dc.contributor.author Hilgert, Neleca
dc.contributor.author Moreno, Felipeca
dc.contributor.author Alsina i Español, Bertaca
dc.contributor.author Petersen, Michael B.ca
dc.contributor.author Kremer, Hannieca
dc.contributor.author Gómez Skarmeta, José Luisca
dc.date.accessioned 2016-01-15T14:34:46Z
dc.date.available 2016-01-15T14:34:46Z
dc.date.issued 2010
dc.description.abstract POU3F4 encodes a POU-domain transcription factor required for inner ear development. Defects in POU3F4 function are associated with X-linked deafness type 3 (DFN3). Multiple deletions affecting up to 900-kb upstream of POU3F4 are found in DFN3 patients, suggesting the presence of essential POU3F4 enhancers in this region. Recently, an inner ear enhancer was reported that is absent in most DFN3 patients with upstream deletions. However, two indications suggest that additional enhancers in the POU3F4 upstream region are required for POU3F4 function during inner ear development. First, there is at least one DFN3 deletion that does not eliminate the reported enhancer. Second, the expression pattern driven by this enhancer does not fully recapitulate Pou3f4 expression in the inner ear. Here, we screened a 1-Mb region upstream of the POU3F4 gene for additional cis-regulatory elements and searched for novel DFN3 mutations in the identified POU3F4 enhancers. We found several novel enhancers for otic vesicle expression. Some of these also drive expression in kidney, pancreas and brain, tissues that are known to express Pou3f4. In addition, we report a new and smallest deletion identified so far in a DFN3 family which eliminates 3.9 kb, comprising almost exclusively the previous reported inner ear enhancer. We suggest that multiple enhancers control the expression of Pou3f4 in the inner ear and these may contribute to the phenotype observed in DFN3 patients. In addition, the novel deletion demonstrates that the previous reported enhancer, although not sufficient, is essential for POU3F4 function during inner ear development.ca
dc.description.sponsorship This work was supported by grants from the Spanish Ministry of Education and Science (BFU2007-60042/BMC, Petri PET2007_0158, CSD2007-00008) and Junta de Andalucía (Proyecto de Excelencia CVI-3488) to JLG-S, and the Oticon Foundation (Denmark) to MBP. CABD is institutionally supported by CSIC, Universidad Pablo de Olavide and Junta de Andalucía.
dc.format.mimetype application/pdfca
dc.identifier.citation Naranjo S, Voesenek K, de la Calle-Mustienes E, Robert-Moreno A, Kokotas H, Grigoriadou M et al. Multiple enhancers located in a 1-Mb region upstream of POU3F4 promote expression during inner ear development and may be required for hearing. Human Genetics. 2010;128(4):411-9. DOI: 10.1007/s00439-010-0864-xca
dc.identifier.doi http://dx.doi.org/10.1007/s00439-010-0864-x
dc.identifier.issn 0340-6717
dc.identifier.uri http://hdl.handle.net/10230/25581
dc.language.iso engca
dc.publisher Springerca
dc.relation.ispartof Human Genetics. 2010;128(4):411-9
dc.relation.projectID info:eu-repo/grantAgreement/ES/2PN/BFU2007-60042
dc.rights © Springer. This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.ca
dc.rights.accessRights info:eu-repo/semantics/openAccessca
dc.subject.other Oïdaca
dc.subject.other Proteïnesca
dc.title Multiple enhancers located in a 1-Mb region upstream of POU3F4 promote expression during inner ear development and may be required for hearingca
dc.type info:eu-repo/semantics/articleca
dc.type.version info:eu-repo/semantics/publishedVersionca

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