# Mechanisms of eukaryotic transcription activation

> **NIH NIH R01** · FRED HUTCHINSON CANCER RESEARCH CENTER · 2020 · $527,403

## Abstract

Summary
Transcription activation, a key step in gene control, is the readout of many signaling pathways controlling cell
growth, development and stress response and defects in activation cause many human diseases and
syndromes. Activation typically results from factors containing activation domains (ADs) binding to coactivator
complexes containing activator binding domains (ABDs). Understanding the nature of ADs, the specificity of
AD-coactivator interactions, and mechanisms of coactivator cooperativity are necessary for understanding the
molecular basis of gene regulation. The long-term goal of this project is to determine mechanisms used by
gene-specific activators and coactivators to regulate RNA polymerase (Pol) II transcription. The objectives of
this proposal are to determine: i) mechanisms of Mediator recruitment and its interaction with ADs, ii)
mechanisms of cooperativity between Mediator and the coactivator SAGA, and iii) what constitutes a functional
AD and determines the AD specificity for different coactivators and promoter types. This work will utilize an
interdisciplinary combination of biochemical, structural, molecular, and computational approaches to examine
transcriptional activation in S. cerevisiae. To understand these mechanisms, we will build upon several
breakthrough concepts and methods developed in the past grant period. We will use a combination of
genomics and biochemistry to identify a new mechanism of Mediator recruitment that is likely used at many
genes. We will use orthogonal approaches to determine how the coactivator SAGA stimulates genome-wide
transcription, either by direct interaction with the Pol II preinitiation complex (PIC) and/or by direct interaction
with Mediator. We will determine the structural basis for AD-Mediator Tail domain interaction using a
combination of biochemical and structural analysis. Finally, we will use a combination of biochemistry,
genomics, and computational analysis to predict AD function and specificity and identify new mechanisms of
AD-coactivator interaction. The expected outcome of these studies will be a molecular understanding of
transcription activator specificity and function, mechanisms used by the coactivators Mediator and SAGA to
promote transcription, and an understanding of how these factors function at different classes of genes –a leap
forward in understanding widely conserved mechanisms of eukaryotic gene regulation.

## Key facts

- **NIH application ID:** 9968281
- **Project number:** 5R01GM075114-15
- **Recipient organization:** FRED HUTCHINSON CANCER RESEARCH CENTER
- **Principal Investigator:** Steven M Hahn
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $527,403
- **Award type:** 5
- **Project period:** 2005-09-01 → 2021-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9968281

## Citation

> US National Institutes of Health, RePORTER application 9968281, Mechanisms of eukaryotic transcription activation (5R01GM075114-15). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9968281. Licensed CC0.

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