# Eavesdropping on the conversation between chromatin and metabolism

> **NIH NIH R35** · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2022 · $381,250

## Abstract

Abstract
Research over the last decades has uncovered epigenetic mechanisms that precisely regulate the genome. For
instance, histone post-translational modifications (PTMs) shape the local chromatin landscape of human cells to
establish permissive and repressive regions within the genome to orchestrate DNA transcription, replication, and
repair. Nevertheless, there is still a great deal that we do not understand about how the cell integrates signals
from inside and outside itself to coordinate proper gene expression. In addition to the classic signaling pathways
that couple metabolism to transcription (e.g., nuclear receptors, kinases), chromatin directly “senses” metabolic
status through the availability of metabolites that are converted to histone PTMs. Since metabolic dysregulation
is a component of nearly every disease, understanding how these altered metabolic pathways impact epigenetic
regulation and vice versa is critical for developing new and effective disease interventions. However, the
incredible complexity and dynamic nature of metabolic pathways and chromatin PTM signaling has made it
difficult to characterize the molecular-level details of this link between metabolism and chromatin. To tackle this
problem, my lab is creating novel chemical tools to determine how a particular subset of histone PTMs called
acylations are regulated by acyl-CoA metabolism and how these PTMs lead to specific effects on gene
expression. We are developing acyl-CoA biosensors to determine how acyl-CoA dynamics change in response
to cellular conditions and how compartmentalization of acyl-CoA metabolism occurs, particularly with respect to
the nuclear compartment and histone acylation. Moreover, our biosensors will similarly expand our
understanding of acyl-CoA metabolism under both normal and disease conditions and will enable the
identification of the acyl-CoA-producing enzymes and acyltransferases that regulate specific histone acylations.
To determine how histone acylations impact gene expression, we are developing affinity-based probes to identify
proteins that bind to histone acylations. By identifying these binding proteins, we will be able to assign specific
gene regulatory functions to these PTMs. With this information, we will be able to develop new therapeutic
strategies to intercept communication between metabolism and the genome at the acyl-CoA and histone
acylation levels to precisely reprogram these signaling pathways in disease.

## Key facts

- **NIH application ID:** 10447802
- **Project number:** 5R35GM143080-02
- **Recipient organization:** UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH
- **Principal Investigator:** Katharine Diehl
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $381,250
- **Award type:** 5
- **Project period:** 2021-07-15 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10447802

## Citation

> US National Institutes of Health, RePORTER application 10447802, Eavesdropping on the conversation between chromatin and metabolism (5R35GM143080-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10447802. Licensed CC0.

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