Nuclear microenvironments modulate transcription from low-affinity enhancers

Albert Tsai, Anand K. Muthusamy, Mariana R.P. Alves, Luke D. Lavis, Robert H. Singer, David L. Stern, Justin Crocker

Research output: Contribution to journalArticle

24 Citations (Scopus)

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.

Original languageEnglish (US)
Article numbere28975
JournaleLife
Volume6
DOIs
StatePublished - Nov 2 2017

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Transcription
Transcription Factors
DNA sequences
Drosophila melanogaster
Transcriptional Activation
Chemical activation
Binding Sites
Kinetics

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

Cite this

Tsai, A., Muthusamy, A. K., Alves, M. R. P., Lavis, L. D., Singer, R. H., Stern, D. L., & Crocker, J. (2017). Nuclear microenvironments modulate transcription from low-affinity enhancers. eLife, 6, [e28975]. https://doi.org/10.7554/eLife.28975

Nuclear microenvironments modulate transcription from low-affinity enhancers. / Tsai, Albert; Muthusamy, Anand K.; Alves, Mariana R.P.; Lavis, Luke D.; Singer, Robert H.; Stern, David L.; Crocker, Justin.

In: eLife, Vol. 6, e28975, 02.11.2017.

Research output: Contribution to journalArticle

Tsai, A, Muthusamy, AK, Alves, MRP, Lavis, LD, Singer, RH, Stern, DL & Crocker, J 2017, 'Nuclear microenvironments modulate transcription from low-affinity enhancers', eLife, vol. 6, e28975. https://doi.org/10.7554/eLife.28975
Tsai A, Muthusamy AK, Alves MRP, Lavis LD, Singer RH, Stern DL et al. Nuclear microenvironments modulate transcription from low-affinity enhancers. eLife. 2017 Nov 2;6. e28975. https://doi.org/10.7554/eLife.28975
Tsai, Albert ; Muthusamy, Anand K. ; Alves, Mariana R.P. ; Lavis, Luke D. ; Singer, Robert H. ; Stern, David L. ; Crocker, Justin. / Nuclear microenvironments modulate transcription from low-affinity enhancers. In: eLife. 2017 ; Vol. 6.
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