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Elife. 2017 Nov 2;6. pii: e28975. doi: 10.7554/eLife.28975.

Nuclear microenvironments modulate transcription from low-affinity enhancers.

Author information

1
Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, United States.
2
European Molecular Biology Laboratory, Heidelberg, Germany.
3
Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, Bronx, United States.
#
Contributed equally

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.

KEYWORDS:

D. melanogaster; Hox genes; biophysics; chromosomes; genes; live imaging; structural biology; super resolution; transcription factors; transcriptional enhancers

PMID:
29095143
PMCID:
PMC5695909
DOI:
10.7554/eLife.28975
[Indexed for MEDLINE]
Free PMC Article

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