@article {45847,
	title = {Low affinity binding site clusters confer Hox specificity and regulatory robustness.},
	journal = {Cell},
	volume = {160},
	year = {2015},
	month = {2015 Jan 15},
	pages = {191-203},
	abstract = {<p>In animals, Hox transcription factors define regional identity in distinct anatomical domains. How Hox genes encode this specificity is a paradox, because different Hox proteins bind with high affinity in\&nbsp;vitro to similar DNA sequences. Here, we demonstrate that the Hox protein Ultrabithorax (Ubx) in complex with its cofactor Extradenticle (Exd) bound specifically to clusters of very low affinity sites in enhancers of the shavenbaby gene of Drosophila. These low affinity sites conferred specificity for Ubx binding in\&nbsp;vivo, but multiple clustered sites were required for robust expression when embryos developed in\&nbsp;variable environments. Although most individual Ubx binding sites are not evolutionarily conserved, the overall enhancer architecture-clusters of low affinity binding sites-is maintained and required for enhancer function. Natural selection therefore works at the level of the enhancer, requiring a particular density of low affinity Ubx sites to confer both specific and robust expression.</p>
},
	issn = {1097-4172},
	doi = {10.1016/j.cell.2014.11.041},
	author = {Crocker, Justin and Abe, Namiko and Rinaldi, Lucrezia and McGregor, Alistair P and Frankel, Nicol{\'a}s and Wang, Shu and Alsawadi, Ahmad and Valenti, Philippe and Plaza, Serge and Payre, Fran{\c c}ois and Mann, Richard S and Stern, David L}
}
