| First Author | Zhao J | Year | 2009 |
| Journal | Hum Mol Genet | Volume | 18 |
| Issue | 16 | Pages | 3090-7 |
| PubMed ID | 19477957 | Mgi Jnum | J:150728 |
| Mgi Id | MGI:3851636 | Doi | 10.1093/hmg/ddp250 |
| Citation | Zhao J, et al. (2009) HnRNP U mediates the long-range regulation of Shh expression during limb development. Hum Mol Genet 18(16):3090-7 |
| abstractText | Transcriptional modulation may be mediated by cis-regulatory elements distant from their target genes. Mutations in a conserved locus about 1 Mb upstream of the Shh coding region often affect Shh expression and are associated with preaxial polydactyly (PPD) defects. To understand the molecular mechanism, we analyzed a novel mouse PPD model with a T-to-A point mutation in this distant locus. A core element of mutation (CEM) with putative enhancer activity was identified by promoter activity assay and shown to contain a matrix attachment region. HnRNP U preferentially bound to the mutant but not the wild-type CEM. Interestingly, HnRNP U also bound to the 5'-UTR of the Shh gene, which was not located in the nuclear matrix in wild-type embryonic cells, as indicated by chromatin immunoprecipitation. We propose that the 5'-UTR of Shh was pulled into the nuclear matrix by HnRNP U when the CEM was mutated, and consequently affected Shh expression. Therefore, distant cis-elements may modulate gene expression by altering HnRNP U's affinity for certain mediator proteins and nuclear relocation. |
