@article {45412,
	title = {Reactivation of developmentally silenced globin genes by forced chromatin looping.},
	journal = {Cell},
	volume = {158},
	year = {2014},
	month = {2014 Aug 14},
	pages = {849-60},
	abstract = {<p>Distal enhancers commonly contact target promoters via chromatin looping. In erythroid cells, the locus control region (LCR) contacts β-type globin genes in a developmental stage-specific manner to\&nbsp;stimulate transcription. Previously, we induced LCR-promoter looping by tethering the self-association domain (SA) of Ldb1 to the β-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 γ-globin promoter in primary adult human erythroblasts increases γ-globin promoter-LCR contacts, stimulating transcription to approximately 85\% of total β-globin synthesis, with a reciprocal reduction in adult β-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\&nbsp;of globin gene transcription for therapeutic applications.</p>
},
	issn = {1097-4172},
	doi = {10.1016/j.cell.2014.05.050},
	author = {Deng, Wulan and Rupon, Jeremy W and Krivega, Ivan and Breda, Laura and Motta, Irene and Jahn, Kristen S and Reik, Andreas and Gregory, Philip D and Rivella, Stefano and Dean, Ann and Blobel, Gerd A}
}
