# Integration of metabolism and chromatin in regulating gene expression in vivo

> **NIH NIH R00** · CASE WESTERN RESERVE UNIVERSITY · 2024 · $249,000

## Abstract

PROJECT SUMMARY (See instructions): 
Understanding the molecular mechanisms of how cells respond to changing environmental cues and 
integrate various signals, especially in the context of an intricate tissue or organism, is a major challenge. In 
the mammalian intestine, inputs from diet and the commensal microbiota can occur in the form of metabolites 
that act on neighboring intestinal epithelial cells and impact physiology. One such class of metabolites are 
short chain fatty acids (SCFAs), which are generated by microbes through the breakdown of dietary fiber. 
Recently, SCFAs have been detected as chemical modifications on histone proteins, called histone 
acylations. While certain histone acylations have been reported to positively regulate transcription, including 
the well-studied histone acetylation, the mechanistic functional role of other acyl marks and especially their 
physiological roles, are largely unknown. In addition, alterations in the chromatin landscape can have 
consequences on the regulation of gene expression and downstream cellular functions. Thus, my overall 
goal is to gain mechanistic understanding of how histone acylations are regulated and govern cell function in 
vivo. My central hypothesis is that different histone acylations have distinct functions in gene regulation 
through playing different roles in particular tissues and gene sets, and that exogenous cues regulate the 
balance of histone acylations that can drive cellular phenotypes. I will use the murine intestinal tract as a 
model system, which will likely elucidate physiological functions and delineate regulatory mechanisms of 
histone acyl marks. During the mentored phase of this award, I focused on the following Aims: (1) Studying 
how acyl reader complexes regulate gene expression under particular cell contexts, (2) Determining how 
histone acylations regulate intestinal epithelial cell fate. In this next independent phase of this award, I will 
continue studying mechanisms of how different acyl marks are regulated and focus on Aim 3: Investigating 
the regulation of histone acylations through cellular metabolism. This proposed work will utilize skills built 
during my postdoctoral training and the mentored phase of this award to foster my success as an independent 
scientist. Together, completion of this research proposal will elucidate the connection between metabolism 
and chromatin and further advance our understanding of the physiological roles of novel histone acyl marks.

## Key facts

- **NIH application ID:** 10932469
- **Project number:** 4R00GM143550-03
- **Recipient organization:** CASE WESTERN RESERVE UNIVERSITY
- **Principal Investigator:** Leah Ashley Gates
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $249,000
- **Award type:** 4N
- **Project period:** 2024-01-01 → 2026-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10932469

## Citation

> US National Institutes of Health, RePORTER application 10932469, Integration of metabolism and chromatin in regulating gene expression in vivo (4R00GM143550-03). Retrieved via AI Analytics 2026-05-29 from https://api.ai-analytics.org/grant/nih/10932469. Licensed CC0.

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