Nuclear microenvironments modulate transcription from low-affinity enhancers
- Janelia Farm Research Campus, Howard Hughes Medical Institute, United States
- European Molecular Biology Laboratory, Germany
Abstract
Transcription factors bind low-affinity DNA sequences for only short durations. It is not clear how brief, low-affinity interactions can drive efficient transcription. Here we report that the transcription factor Ultrabithorax (Ubx) utilizes low-affinity binding sites in the Drosophila melanogaster shavenbaby (svb) locus and related enhancers in nuclear microenvironments of high Ubx concentrations. Related enhancers colocalize to the same microenvironments independently of their chromosomal location, suggesting that microenvironments are highly differentiated transcription domains. Manipulating the affinity of svb enhancers revealed an inverse relationship between enhancer affinity and Ubx concentration required for transcriptional activation. The Ubx cofactor, Homothorax (Hth), was co-enriched with Ubx near enhancers that require Hth, even though Ubx and Hth did not co-localize throughout the nucleus. Thus, microenvironments of high local transcription factor and cofactor concentrations could help low-affinity sites overcome their kinetic inefficiency. Mechanisms that generate these microenvironments could be a general feature of eukaryotic transcriptional regulation.
Data availability
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Tsai A, Muthusamy A, Alves M, Lavis L, Singer R, Stern D, Crocker JAvailable at Dryad Digital Repository under a CC0 Public Domain Dedication.
Article and author information
Author details
Funding
Damon Runyon Cancer Research Foundation (DRG 2220-15)
- Albert Tsai
National Institutes of Health (U01-EB21236)
- Robert H Singer
Howard Hughes Medical Institute
- Albert Tsai
- Anand K Muthusamy
- Luke D Lavis
- Robert H Singer
- David L Stern
- Justin Crocker
European Molecular Biology Laboratory
- Mariana RP Alves
- Justin Crocker
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2017, Tsai et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Nuclear microenvironments modulate transcription from low-affinity enhancers
eLife 6:e28975.
https://doi.org/10.7554/eLife.28975
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