# Characterizing Structure-Function Relationships in Archaeal-to-Eukaryotic Chromatin Evolution

> **NIH NIH F32** · UNIVERSITY OF COLORADO · 2020 · $65,310

## Abstract

Project Summary
Current organization of the “Tree of Life” arranges organisms in to three domains: Bacteria, Archaea, and
Eukaryota. Eukaryotes package genomes that are typically orders of magnitude larger than both prokaryotic
domains by utilizing histone proteins to form nucleosomes. Originally, histones were only observed in
eukaryotes, but studies over the past two decades have identified a plethora of histone sequences in many
archaeal species and that these histones can package DNA with “nucleosome-like” constructs, which we call
“archaeasomes”. Futhermore, some histone sequences encoded in the Asgard superphylum of Archaea have
been identified to contain disordered and positively charged histone tails, a trait rarely observed in archaea but
predominant in eukaryotes. These observations provided evidence for the hypothesis that Archaea, and
specifically Asgards, bridge the evolutionary gap between prokaryotic and eukaryotic life. However, little is
known about the solution structure of archaeasome constructs and how they regulate gene expression in the
cell, and even less is understood about how different histone features, such as highly charged tails, contribute
to archaeasome stability and influenced archaeasome-to-nucleosome evolution. In this proposal, we aim to
characterize the inherent structure-dynamics-function relationship between archaeasome stability and
cellular behaviors, such as growth rates and transcription regulation. Furthermore, we will characterize
the chromatin-forming ability of putative Asgard histones and shed light on how disordered and
positively charged tails aide in regulating the formation of elongated archaeasome complexes. In the
first aim, we will combine computational models with in vitro biophysical characterization techniques, namely
cryoEM and analytical ultracentrifuation (AUC), to determine archaeasome structures of varying sizes. We also
identify key sites within archaeal histone proteins that may be mutated to allow for the formation of larger
archaeasome constructs, and we will collaborate with cell biologists to correlate in vitro stabilization with in vivo
transcription regulation and cell growth. For our second aim, Asgard species cannot currently be cultured, so
we will utilize the in vitro methods of cryoEM, MNase digestion, and AUC to characterize the solution structure
and accessibility dynamics of chromatin formed by Asgard histones, which are hypothesized to be the closest
known ancestor to eukaryotic histones. We will express Asgard histones with and without the highly charged
tails to determine the effect of tail sequence on chromatin structure and dynamics and infer their role in
archaeasome-to-nucleosome evolution.

## Key facts

- **NIH application ID:** 10069156
- **Project number:** 1F32GM137496-01A1
- **Recipient organization:** UNIVERSITY OF COLORADO
- **Principal Investigator:** Samuel Bowerman
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $65,310
- **Award type:** 1
- **Project period:** 2020-09-01 → 2021-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10069156

## Citation

> US National Institutes of Health, RePORTER application 10069156, Characterizing Structure-Function Relationships in Archaeal-to-Eukaryotic Chromatin Evolution (1F32GM137496-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10069156. Licensed CC0.

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