dc.creator | Jeong, Yongsu | |
dc.creator | Coluccio Leskow, Federico | |
dc.creator | El Jaick, Kenia | |
dc.creator | Roessler, Erich | |
dc.creator | Muenke, Maximilian | |
dc.creator | Yocum, Anastasia | |
dc.creator | Dubourg, Christele | |
dc.creator | Li, Xue | |
dc.creator | Geng, Xin | |
dc.creator | Oliver, Guillermo | |
dc.creator | Epstein, Douglas J. | |
dc.date.accessioned | 2019-09-18T19:21:59Z | |
dc.date.accessioned | 2022-10-15T11:22:46Z | |
dc.date.available | 2019-09-18T19:21:59Z | |
dc.date.available | 2022-10-15T11:22:46Z | |
dc.date.created | 2019-09-18T19:21:59Z | |
dc.date.issued | 2008-11 | |
dc.identifier | Jeong, Yongsu; Coluccio Leskow, Federico; El Jaick, Kenia; Roessler, Erich; Muenke, Maximilian; et al.; Regulation of a remote Shh forebrain enhancer by the Six3 homeoprotein; Nature Publishing Group; Nature Genetics; 40; 11; 11-2008; 1348-1353 | |
dc.identifier | 1061-4036 | |
dc.identifier | http://hdl.handle.net/11336/83860 | |
dc.identifier | CONICET Digital | |
dc.identifier | CONICET | |
dc.identifier.uri | https://repositorioslatinoamericanos.uchile.cl/handle/2250/4380363 | |
dc.description.abstract | In humans, SHH haploinsufficiency results in holoprosencephaly (HPE), a defect in anterior midline formation. Despite the importance of maintaining SHH transcript levels above a critical threshold, we know little about the upstream regulators of SHH expression in the forebrain. Here we describe a rare nucleotide variant located 460 kb upstream of SHH in an individual with HPE that resulted in the loss of Shh brain enhancer-2 (SBE2) activity in the hypothalamus of transgenic mouse embryos. Using a DNA affinity-capture assay, we screened the SBE2 sequence for DNA-binding proteins and identified members of the Six3 and Six6 homeodomain family as candidate regulators of Shh transcription. Six3 showed reduced binding affinity for the mutant compared to the wild-type SBE2 sequence. Moreover, Six3 with HPE-causing alterations failed to bind and activate SBE2. These data suggest a direct link between Six3 and Shh regulation during normal forebrain development and in the pathogenesis of HPE. | |
dc.language | eng | |
dc.publisher | Nature Publishing Group | |
dc.relation | info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1038/ng.230 | |
dc.relation | info:eu-repo/semantics/altIdentifier/url/https://www.nature.com/articles/ng.230 | |
dc.rights | https://creativecommons.org/licenses/by-nc-sa/2.5/ar/ | |
dc.rights | info:eu-repo/semantics/restrictedAccess | |
dc.subject | Sonic hedgehog | |
dc.subject | Mouse development | |
dc.subject | forebrain enhancer | |
dc.subject | Six | |
dc.title | Regulation of a remote Shh forebrain enhancer by the Six3 homeoprotein | |
dc.type | info:eu-repo/semantics/article | |
dc.type | info:ar-repo/semantics/artículo | |
dc.type | info:eu-repo/semantics/publishedVersion | |