| First Author | Deng W | Year | 2014 |
| Journal | Cell | Volume | 158 |
| Issue | 4 | Pages | 849-860 |
| PubMed ID | 25126789 | Mgi Jnum | J:214585 |
| Mgi Id | MGI:5603449 | Doi | 10.1016/j.cell.2014.05.050 |
| Citation | Deng W, et al. (2014) Reactivation of developmentally silenced globin genes by forced chromatin looping. Cell 158(4):849-60 |
| abstractText | Distal enhancers commonly contact target promoters via chromatin looping. In erythroid cells, the locus control region (LCR) contacts beta-type globin genes in a developmental stage-specific manner to stimulate transcription. Previously, we induced LCR-promoter looping by tethering the self-association domain (SA) of Ldb1 to the beta-globin promoter via artificial zinc fingers. Here, we show that targeting the SA to a developmentally silenced embryonic globin gene in adult murine erythroblasts triggers its transcriptional reactivation. This activity depends on the LCR, consistent with an LCR-promoter looping mechanism. Strikingly, targeting the SA to the fetal gamma-globin promoter in primary adult human erythroblasts increases gamma-globin promoter-LCR contacts, stimulating transcription to approximately 85% of total beta-globin synthesis, with a reciprocal reduction in adult beta-globin expression. Our findings demonstrate that forced chromatin looping can override a stringent developmental gene expression program and suggest a novel approach to control the balance of globin gene transcription for therapeutic applications. |
