# Chromosome Archae-tecture: Conserved principles of chromosome organization

> **NIH NIH R01** · TRUSTEES OF INDIANA UNIVERSITY · 2021 · $311,193

## Abstract

PROJECT SUMMARY
The three-dimensional organization of DNA within cells is of profound importance for the appropriate and timely
execution of gene expression programs. Recent advances in experimental approaches have allowed the
elucidation of the conformation of chromosomes of bacteria and eukaryotes with unprecedented resolution.
Bacterial chromosomes are organized into locally folded units and chromosome arms either side of the origin of
replication are juxtaposed processively by the action of SMC proteins. In contrast, metazoa have large-scale
domains along the linear order of the chromosome, these fall into two distinct types that exclusively associate to
form two distinct classes of higher-order compartment. To date, essentially nothing is known about the
conformation of chromosomes from organisms in the third domain of life, the Archaea. Many aspects of the
information processing (DNA replication, gene transcription) machineries of archaea and eukaryotes are
fundamentally related and distinct from those of bacteria. This is despite the prokaryotic nature of archaea, their
morphological similarities to bacteria and the presence of simple circular chromosomes, as in many bacteria.
Strikingly, preliminary data reveal that the chromosomes of hyperthermophilic archaea of the genus Sulfolobus,
like eukaryotes, and distinct from bacteria, possess a large-scale domain architecture with higher-order
organization into two distinct classes of compartment. This provocative observation suggests that the
fundamental logic of chromosome organization may predate the bifurcation of archaeal and eukaryotic lineages.
The preliminary data will be extended to provide a high-resolution 4-D roadmap of the dynamic structure of the
archaeal genome. A novel SMC-related protein is implicated in coordinating the structure of the genome and its
role will be investigated both in vivo and in vitro using a combination of genetic and biochemical approaches.
Finally, the causality of the interplay between the cellular gene expression program and chromosome
architecture will be determined.
Taken as a whole, this work will exploit a unique and simple model system to elucidate the mechanisms and
evolution of the conserved principles governing the higher-order organization of genomes.

## Key facts

- **NIH application ID:** 10064146
- **Project number:** 5R01GM135178-02
- **Recipient organization:** TRUSTEES OF INDIANA UNIVERSITY
- **Principal Investigator:** Stephen David Bell
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $311,193
- **Award type:** 5
- **Project period:** 2019-12-02 → 2023-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10064146

## Citation

> US National Institutes of Health, RePORTER application 10064146, Chromosome Archae-tecture: Conserved principles of chromosome organization (5R01GM135178-02). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/10064146. Licensed CC0.

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