# Molecular analysis of eukaryotic transcription

> **NIH NIH R01** · FRED HUTCHINSON CANCER RESEARCH CENTER · 2020 · $646,191

## Abstract

Summary
Transcriptional regulation is a primary target of many signaling and developmental pathways and regulation of
transcription is one of the key steps in control of cell growth, differentiation and development. Published studies
suggest at least two classes of core promoters that differ in whether they contain a consensus TATA element
and in their requirements for the coactivator complexes TFIID and SAGA. Available evidence suggests that
these promoter types differ in the mechanism of interaction with the basal factors, in regulation by chromatin
and its modifications, and in their response to transcription regulators. Since most mechanistic studies to date
have been conducted on TATA-containing promoters, little is understood about the mechanisms of initiation
and regulation at the ~80% of genes lacking TATAs, leaving a large gap in understanding how most RNA
polymerase (Pol) II transcribed genes are regulated. The long term goals of this project are to determine the
mechanisms of RNA Pol II transcription initiation and how these mechanisms are utilized as targets for gene
regulation. The rationale for this work is that determining the mechanisms used in initiation and its regulation
will form the molecular basis for understanding defects in transcription disorders leading to many types of
human disease. The objectives of this application are to determine the mechanisms utilized for initiation and
regulation at TATA-less promoters, the specificity, function, and overlap of the coactivators TFIID and SAGA
and the mechanism of DNA opening, transcription start site (TSS) scanning and TSS recognition during the
dynamic process of transcription initiation. Our proposed research will utilize biochemical, molecular genetic,
genomics, and biophysical approaches to examine transcriptional regulation in S. cerevisiae because the
advantages in molecular genetics and biochemistry in this system allow rapid and precise mechanistic
investigations. The basal machinery, TFIID and SAGA are all conserved so that results from the yeast system
are directly relevant to human gene regulatory mechanisms. Recent findings and new approaches have called
into question the initial TFIID and SAGA-regulated characterization of promoters and suggest a potentially
large overlap between the sets of genes modulated by these factors. We will use a new approach we
developed to map the genome-wide location, specificity and functional importance of these two coactivators on
genome-wide expression. We will utilize a new in vitro system that transcribes TATA-less promoters to
investigate biochemical mechanisms of these coactivators and how they are regulated. We will also use an
innovative single molecule approach to investigate the dynamic mechanism of transcription initiation in the Pol
II system at TATA-containing promoters. Our proposed research is significant because it will lead to a vertical
advance in understanding the role of two conserved coactivators that together regu...

## Key facts

- **NIH application ID:** 9902500
- **Project number:** 5R01GM053451-25
- **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:** $646,191
- **Award type:** 5
- **Project period:** 1995-09-30 → 2021-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9902500

## Citation

> US National Institutes of Health, RePORTER application 9902500, Molecular analysis of eukaryotic transcription (5R01GM053451-25). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9902500. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*