Biological Sciences Division
Published November 9, 2018 | Version v1
Journal article Open

Tuned polymerization of the transcription factor yan limits off-DNA sequestration to confer context-specific repression

Creators

  • 1. University of Chicago

Description

During development, transcriptional complexes at enhancers regulate gene expression in complex spatiotemporal patterns. To achieve robust expression without spurious activation, the affinity and specificity of transcription factor–DNA interactions must be precisely balanced. Protein–protein interactions among transcription factors are also critical, yet how their affinities impact enhancer output is not understood. The Drosophila transcription factor Yan provides a well-suited model to address this, as its function depends on the coordinated activities of two independent and essential domains: the DNA-binding ETS domain and the self-associating SAM domain. To explore how protein–protein affinity influences Yan function, we engineered mutants that increase SAM affinity over four orders of magnitude. This produced a dramatic subcellular redistribution of Yan into punctate structures, reduced repressive output and compromised survival. Cell-type specification and genetic interaction defects suggest distinct requirements for polymerization in different regulatory decisions. We conclude that tuned protein–protein interactions enable the dynamic spectrum of complexes that are required for proper regulation.

Data availability

A published ChIP dataset was used in this study: Webber JL, Zhang J, Cote L, Vivekanand P, Ni X, Zhou J, Nègre N, Carthew RW, White KP, Rebay I. Genetics. 2013. The relationship between long-range chromatin occupancy and polymerization of the Drosophila ETS family transcriptional repressor Yan. Raw data for this published study are available as a GEO dataset (Series: GSE34038 and GSE34040). All other data analysed during this study are included in the manuscript and supporting files. Source data files have been provided for Figures 1 and 3.

The following previously published data sets were used:

Webber JL, Zhang J, Cote L, Vivekanand P, Ni X, Zhou J, Nègre N, Carthew RW, White KP, Rebay I (2013) NCBI Gene Expression Omnibus ID GSE34038. The relationship between long-range chromatin occupancy and polymerization of the Drosophila ETS family transcriptional repressor Yan. https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE34038

Webber JL, Zhang J, Cote L, Vivekanand P, Ni X, Zhou J, Nègre N, Carthew RW, White KP, Rebay I (2013) NCBI Gene Expression Omnibus ID GSE34040. The relationship between long-range chromatin occupancy and polymerization of the Drosophila ETS family transcriptional repressor Yan. https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE34040

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Additional details

Identifiers

DOI
10.7554/eLife.37545
Other
oai:uchicago.tind.io:9894

Funding

National Institutes of Health
R01 GM080372
National Science Foundation
REU 1659490
National Institutes of Health
P30 CA014599
National Institutes of Health
T32 GM007183
National Institutes of Health
2T32 HL007381-36A1
American Heart Association
12POST12040225
American Heart Association
15POST22660028

UChicago Information

Division(s)
Biological Sciences Division
Department(s)
Ben May Department for Cancer Research, Biochemistry and Molecular Biology, Development, Regeneration, and Stem Cell Biology