A combination of transcription factors mediates inducible interchromosomal contacts
- University of Washington, United States
Abstract
The genome forms specific three-dimensional contacts in response to cellular or environmental conditions. However, it remains largely unknown which proteins specify and mediate such contacts. Here we describe an assay, MAP-C (Mutation Analysis in Pools by Chromosome conformation capture), that simultaneously characterizes the effects of hundreds of cis or trans-acting mutations on a chromosomal contact. Using MAP-C, we show that inducible interchromosomal pairing between HAS1pr-TDA1pr alleles in saturated cultures of Saccharomyces yeast is mediated by three transcription factors, Leu3, Sdd4 (Ypr022c), and Rgt1. The coincident, combined binding of all three factors is strongest at the HAS1pr-TDA1pr locus and is also specific to saturated conditions. We applied MAP-C to further explore the biochemical mechanism of these contacts, and find they require the structured regulatory domain of Rgt1, but no known interaction partners of Rgt1. Altogether, our results demonstrate MAP-C as a powerful method for dissecting the mechanistic basis of chromosome conformation.
Article and author information
Author details
Funding
National Institutes of Health (U54 DK107979)
- Jay Shendure
National Science Foundation (Graduate Research Fellowship DGE-1256082)
- Seungsoo Kim
Howard Hughes Medical Institute (Investigator)
- Jay Shendure
Canadian Institute for Advanced Research (Senior Fellow (Genetic Networks Program))
- Maitreya J Dunham
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2019, Kim 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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A combination of transcription factors mediates inducible interchromosomal contacts
eLife 8:e42499.
https://doi.org/10.7554/eLife.42499
