![[feed]](/style/images/feed-icon-14x14.png){kind=icon}
Tools
Tools
![[thumbnail of 12630oa.pdf]](https://edoc.mdc-berlin.de/style/images/fileicons/application_pdf.png) |
PDF
- Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
2MB |
| Item Type: | Article |
|---|---|
| Title: | A misplaced lncRNA causes brachydactyly in humans |
| Creators Name: | Maass, P.G., Rump, A., Schulz, H., Stricker, S., Schulze, L., Platzer, K., Aydin, A., Tinschert, S., Goldring, M.B., Luft, F.C. and Bähring, S. |
| Abstract: | Translocations are chromosomal rearrangements that are frequently associated with a variety of disease states and developmental disorders. We identified 2 families with brachydactyly type E (BDE) resulting from different translocations affecting chromosome 12p. Both translocations caused downregulation of the parathyroid hormone-like hormone (PTHLH) gene by disrupting the cis-regulatory landscape. Using chromosome conformation capturing, we identified a regulator on chromosome 12q that interacts in cis with PTHLH over a 24.4-megabase distance and in trans with the sex-determining region Y-box 9 (SOX9) gene on chromosome 17q. The element also harbored a long noncoding RNA (lncRNA). Silencing of the lncRNA, PTHLH, or SOX9 revealed a feedback mechanism involving an expression-dependent network in humans. In the BDE patients, the human lncRNA was upregulated by the disrupted chromosomal association. Moreover, the lncRNA occupancy at the PTHLH locus was reduced. Our results document what we believe to be a novel in cis- and in trans-acting DNA and lncRNA regulatory feedback element that is reciprocally regulated by coding genes. Furthermore, our findings provide a systematic and combinatorial view of how enhancers encoding lncRNAs may affect gene expression in normal development. |
| Keywords: | Brachydactyly, Gene Expression Regulation, Gene Silencing, Genetic Loci, Genetic Translocation, Long Untranslated RNA, Pair 12 Human Chromosomes, Pair 17 Human Chromosomes, Parathyroid Hormone-Related Protein, SOX9 Transcription Factor, Transgenic Mice, Animals, Mice |
| Source: | Journal of Clinical Investigation |
| ISSN: | 0021-9738 |
| Publisher: | American Society for Clinical Investigation |
| Volume: | 122 |
| Number: | 11 |
| Page Range: | 3990-4002 |
| Date: | 1 November 2012 |
| Official Publication: | https://doi.org/10.1172/JCI65508 |
| PubMed: | View item in PubMed |
Repository Staff Only: item control page
