Nuclear microenvironments modulate transcription from low-affinity enhancers

• DOI: 10.7554/elife.28975
• Publication Date: 2017-11-02T15:06:33Z
• Authors: Albert Tsai; Anand K Muthusamy; Mariana RP Alves; Luke D Lavis; Robert H Singer; David L Stern; Justin Crocker
• Keywords: Ultrabithorax; Transcription; engrailed

Transcription factors bind low-affinity DNA sequences for only short durations. It is not clear how brief, interactions can drive efficient transcription. Here, we report that the transcription factor Ultrabithorax (Ubx) utilizes binding sites in Drosophila melanogaster shavenbaby (svb) locus and related enhancers nuclear microenvironments of high Ubx concentrations. Related colocalize to same independently their chromosomal location, suggesting are highly differentiated domains. Manipulating affinity svb revealed an inverse relationship between enhancer concentration required transcriptional activation. The cofactor, Homothorax (Hth), was co-enriched with near require Hth, even though Hth did co-localize throughout nucleus. Thus, local cofactor concentrations could help overcome kinetic inefficiency. Mechanisms generate these be a general feature eukaryotic regulation.