Nuclear microenvironments modulate transcription from low-affinity enhancers
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...
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doaj-a145c2cd935c4eba81ff6c682d5bea352021-05-05T13:54:53ZengeLife Sciences Publications LtdeLife2050-084X2017-11-01610.7554/eLife.28975Nuclear microenvironments modulate transcription from low-affinity enhancersAlbert Tsai0https://orcid.org/0000-0002-1643-0780Anand K Muthusamy1Mariana RP Alves2https://orcid.org/0000-0002-0796-2101Luke D Lavis3Robert H Singer4https://orcid.org/0000-0002-6725-0093David L Stern5https://orcid.org/0000-0002-1847-6483Justin Crocker6https://orcid.org/0000-0002-5113-0476Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, United StatesJanelia Research Campus, Howard Hughes Medical Institute, Ashburn, United StatesEuropean Molecular Biology Laboratory, Heidelberg, GermanyJanelia Research Campus, Howard Hughes Medical Institute, Ashburn, United StatesJanelia Research Campus, Howard Hughes Medical Institute, Ashburn, United States; Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, Bronx, United StatesJanelia Research Campus, Howard Hughes Medical Institute, Ashburn, United StatesJanelia Research Campus, Howard Hughes Medical Institute, Ashburn, United States; European Molecular Biology Laboratory, Heidelberg, GermanyTranscription 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.https://elifesciences.org/articles/28975transcription factorsHox genestranscriptional enhancerssuper resolutionlive imaging |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Albert Tsai Anand K Muthusamy Mariana RP Alves Luke D Lavis Robert H Singer David L Stern Justin Crocker |
spellingShingle |
Albert Tsai Anand K Muthusamy Mariana RP Alves Luke D Lavis Robert H Singer David L Stern Justin Crocker Nuclear microenvironments modulate transcription from low-affinity enhancers eLife transcription factors Hox genes transcriptional enhancers super resolution live imaging |
author_facet |
Albert Tsai Anand K Muthusamy Mariana RP Alves Luke D Lavis Robert H Singer David L Stern Justin Crocker |
author_sort |
Albert Tsai |
title |
Nuclear microenvironments modulate transcription from low-affinity enhancers |
title_short |
Nuclear microenvironments modulate transcription from low-affinity enhancers |
title_full |
Nuclear microenvironments modulate transcription from low-affinity enhancers |
title_fullStr |
Nuclear microenvironments modulate transcription from low-affinity enhancers |
title_full_unstemmed |
Nuclear microenvironments modulate transcription from low-affinity enhancers |
title_sort |
nuclear microenvironments modulate transcription from low-affinity enhancers |
publisher |
eLife Sciences Publications Ltd |
series |
eLife |
issn |
2050-084X |
publishDate |
2017-11-01 |
description |
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. |
topic |
transcription factors Hox genes transcriptional enhancers super resolution live imaging |
url |
https://elifesciences.org/articles/28975 |
work_keys_str_mv |
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1721460517240832000 |