# Mechanisms of transcriptional regulation and transcription factor specificity

> **NIH NIH R35** · FRED HUTCHINSON CANCER CENTER · 2022 · $1,121,571

## Abstract

Summary
Precise regulation of transcription is required for many cellular processes and misregulation of
gene expression is linked to many human diseases. In prior work, great progress has been
made in identifying important mechanisms and principles of transcriptional regulation. With this
background, and using new technologies and approaches, this is an excellent time to tackle the
next set of fundamental problems in gene regulation that have been difficult to address in prior
work. Two related and important questions in the transcription field are: what are the primary
mechanisms of gene regulation by sequence-specific transcription factors? and, how do these
factors cooperate to orchestrate transcription of cellular genes? To address these questions, we
will focus on three areas involving transcription factor and coactivator specificity and the
activation mechanisms used at many genes: (i) Mechanisms leading to the genome-wide
specificities of the coactivators TFIID and SAGA. Differential use of these coactivators defines
two fundamental gene classes that dictate the mechanisms of preinitiation complex (PIC)
assembly and the response to transcription factors and chromatin. (ii) The gene-specific
functions of the coactivator Mediator in transcriptional regulation. At least two distinct pathways
are used by transcription factors to modulate Mediator function that are transcription factor and
promoter-specific, but the molecular basis of these mechanisms is not well understood. (iii)
Mechanisms of transcription activator specificity and function. We will broaden our current
studies on the function of acidic activation domains to examine mechanisms used by other
widely used activator types and to examine how transcription factors bound at native
UAS/enhancer elements cooperate. To address these fundamental problems, as in past work,
we will use a combination of methods and technologies that include molecular, biochemical,
genomic, computational, and structural approaches. In combination with our strong preliminary
results, these new approaches and directions will reveal important conserved mechanisms and
principles that illustrate how transcription factors, coactivators, chromatin, and the basal
transcription machinery work together to modulate genome-wide transcription.

## Key facts

- **NIH application ID:** 10397115
- **Project number:** 6R35GM140823-02
- **Recipient organization:** FRED HUTCHINSON CANCER CENTER
- **Principal Investigator:** Steven M Hahn
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $1,121,571
- **Award type:** 6
- **Project period:** 2021-05-01 → 2026-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10397115

## Citation

> US National Institutes of Health, RePORTER application 10397115, Mechanisms of transcriptional regulation and transcription factor specificity (6R35GM140823-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10397115. Licensed CC0.

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