# Mechanisms of coordinate gene regulation by transcription factors

> **NIH NIH R35** · UNIVERSITY OF CONNECTICUT SCH OF MED/DNT · 2021 · $410,000

## Abstract

ABSTRACT
Many of the molecular mechanisms underlying well-characterized robust and rapidly inducible transcriptional
responses are shared among other systems, so we use the transcriptional response to estrogen treatment as a
model to study gene regulation. We use rapid kinetic regulation and perturbation of transcription cascades,
transcription factors, and cofactors to identify key mechanisms, genes, and regulatory elements that are critical
for estrogen signaling. Transcription factors act as activators or repressors and interface with a constellation of
accessory cofactors to regulate distinct steps in the transcription to coordinate gene expression, but the
molecular functions of the vast majority of transcription factors remain uncharacterized. We will use molecular
genomics and computational methods to classify transcription factors by their molecular function, as opposed
to broad activator and repressor classes, in order to understand the context specificity of gene regulation. We
recently found that the estrogen receptor transcription factor may compete with other transcription factors for
limiting cofactors to mediate estrogen-induced repression. We will develop light inducible dominant negative
peptide inhibitors to test various models of repression and address the challenges of studying estrogen-
repressed genes. The genes and regulatory elements that are downstream of the first wave of transcriptional
response are critical for propagating regulatory cascades. We will generate high temporal resolution time
course data and implement statistical modeling approaches to identify effector genes and regulatory elements
that are critical for estrogen signaling. Our research will continue to reveal basic principles and rules that
govern transcription factor specificity in order to someday understand how genetics, nutrition, and
environmental factors contribute to variation in transcriptional programs that can lead to disease states or
ineffective therapies.

## Key facts

- **NIH application ID:** 10441975
- **Project number:** 7R35GM128635-04
- **Recipient organization:** UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
- **Principal Investigator:** Michael Joseph Guertin
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $410,000
- **Award type:** 7
- **Project period:** 2021-08-01 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10441975

## Citation

> US National Institutes of Health, RePORTER application 10441975, Mechanisms of coordinate gene regulation by transcription factors (7R35GM128635-04). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10441975. Licensed CC0.

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