# COOPERATIVITY AND COLLECTIVE BINDING IN TRANSCRIPTION FACTOR-DNA INTERACTIONS

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 2020 · $390,496

## Abstract

Transcription factors shape gene expression by binding to genomic cis-regulatory elements and
then recruiting nucleosome remodeling factors, the RNA polymerase holoenyzme, and other
transcriptional coactivators. What determines where a transcription factor binds in vivo? For
most eukaryotic transcription factors (TFs), the answer to this question is not known. We have
recently analyzed two yeast bHLH proteins, Cbf1 and Tye7, which have nearly identical DNA
binding preferences in vitro, but bind at almost completely non-overlapping target loci in vivo.
We found that Cbf1 utilizes homotypic cooperativity to achieve its specificity, while Tye7 binds in
a TF collective, a phenomenon that has been described only recently in Drosophila, but is
poorly understood.
We hypothesize that homotypic cooperativity and collective binding are widely used by
eukaryotic TFs to achieve their specificities in vivo. We will test this hypothesis by quantifying
the contribution of these two mechanisms to the in vivo binding of all yeast transcription factors.
We will also dissect a small number of these complexes in detail. We will investigate the
binding specificity of the human bHLH transcription factor Usf1, which is a candidate drug target
because of its involvement in obesity and metabolic disease. The completion of this work will
deepen our understanding of the factors that govern the in vivo specificities of transcription
factors. Furthermore, by gaining an understanding of the protein-protein contacts that regulate
Usf1 binding, we will uncover interactions that can be disrupted for therapeutic benefit.

## Key facts

- **NIH application ID:** 9937822
- **Project number:** 5R01GM123203-03
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Robi D Mitra
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $390,496
- **Award type:** 5
- **Project period:** 2018-06-21 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9937822

## Citation

> US National Institutes of Health, RePORTER application 9937822, COOPERATIVITY AND COLLECTIVE BINDING IN TRANSCRIPTION FACTOR-DNA INTERACTIONS (5R01GM123203-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9937822. Licensed CC0.

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