# Regulation of Archaeal Transcription

> **NIH NIH R35** · COLORADO STATE UNIVERSITY · 2022 · $363,689

## Abstract

Project Summary/Abstract
The essential multi-subunit RNA polymerases are regulated at each stage of the transcription
cycle to control gene expression in each Domain. In many cases the rate limiting step of gene
expression is during transcription elongation, but major knowledge gaps remain in our
understanding of post-initiation regulation of transcription. Our studies directly address
outstanding questions of transcription regulation in archaeal and eukaryotic cells. Our
overarching goals are to establish molecular mechanisms that regulate post-initiation activities
of RNAP, and establish the regulation imposed by histone-based chromatin on gene
expression. How does altering the chromatin-landscape alter gene expression? How, in
molecular detail, do factors that modify the activities of RNA polymerase accelerate transcription
on histone-bound DNA? How can the otherwise extremely stable transcription elongation
complex be disrupted to terminate transcription accurately? These complex challenges demand
continued attention to define the foundational mechanisms underlying gene expression and the
aberrant gene expression associated with disease states and cancer.
We defined that archaeal transcription and chromatin systems are closely related, yet minimal
versions of the component complex eukaryotic transcription systems. We have described the
complete archaeal transcription cycle and defined three mechanisms that control transcription
termination decisions, each of which reveals similarities with bacterial and eukaryotic
termination mechanisms and demands continued experimentation to delineate conserved
mechanisms to disrupt the transcription elongation complex. Our understanding of how
chromatin structure regulates gene expression is also incomplete. We will leverage the
simplicity of single-histone chromatin formed with native histones and histone-variants to
establish the regulation imposed by extended chromatin structures on a genome-wide level. We
will also describe the molecular activities of conserved archaeal-eukaryotic transcription factors
that modify RNA polymerase and accelerate transcription through histone-bound DNA.

## Key facts

- **NIH application ID:** 10324749
- **Project number:** 1R35GM143963-01
- **Recipient organization:** COLORADO STATE UNIVERSITY
- **Principal Investigator:** Thomas James Santangelo
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $363,689
- **Award type:** 1
- **Project period:** 2022-05-16 → 2027-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10324749

## Citation

> US National Institutes of Health, RePORTER application 10324749, Regulation of Archaeal Transcription (1R35GM143963-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10324749. Licensed CC0.

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