# Investigate the molecular mechanisms of the interplay between cell metabolism and histone modification in ethylene signaling in Arabadopsis

> **NIH NIH R01** · UNIVERSITY OF TEXAS AT AUSTIN · 2022 · $334,989

## Abstract

Project Summary
Nuclear enzymes, chromatin and its modifications mediate the responses of cells and organisms to
dynamic environments. Chromatin remodeling influences gene expression by providing transcription
factors and the transcription machinery with dynamic access to an otherwise tightly packaged genome.
Many chromatin-modifying enzymes require metabolites as cofactors; therefore, the cell metabolic state
can influence chromatin structure and epigenetic processes. However, little is known about how metabolic
states and chromatin regulation are coordinated to allow cells and organisms to respond to environmental
conditions. We are using Arabidopsis to study the metabolic states and chromatin regulation in ethylene
signaling. Our group pioneered the study of histone regulation in ethylene signaling. The ethylene signal is
perceived on the endoplasmic reticulum (ER) membrane, and the cleavage and nuclear translocation of EIN2
mediates the signal from the ER membrane to the nucleus. The EIN2 C-terminus (EIN2-C) is cleaved and
translocated to the nucleus to initiate the ethylene response. During the last funding period, we
discovered that EIN2, an essential signaling factor, is also a key component of the histone
modification that directly regulates H3K14Ac and H3K23Ac to mediate the transcriptional response
to ethylene. EIN2 is thus the direct link between ethylene signaling and chromatin regulation. We
also identified a noncanonical histone acetyltransferase (HAT) domain-containing protein EHAT that
directly interacts with the EIN2-C in the nucleus. Our preliminary data strongly suggest that EHAT links
EIN2-mediated ethylene signaling with EIN2-meidated regulation of histone acetylation. Strikingly, our new
data provide solid evidence that the pyruvate dehydrogenase complex, which converts pyruvate
to acetyl-CoA, the acetyl-donor of histone acetylation, interacts with EIN2-C and that the subunits
of the complex can translocate from the mitochondria to the nucleus in response to ethylene. This
new discovery provides a strong rational for the hypothesis that acetyl-CoA biosynthesis is involved in the
EIN2-mediated interplay between chromatin regulation and ethylene signaling. In this proposal, we will
study metabolic states and chromatin regulation in ethylene signaling by focusing on the following specific
aims: (1) elucidate the detailed mechanisms governing EIN2-dependent histone modification in response
to ethylene; (2) investigate the function of the metabolic enzyme pyruvate dehydrogenase in EIN2-
mediated chromatin and transcriptional regulation in response to ethylene, and (3) elucidate the molecular
mechanisms by which the EIN2-C is translocated to the nucleus in response to ethylene. Our work will
have broad implications as dysfunctions of nuclear processes contribute directly to cancer progression and
genetic disorders and imbalances between metabolism and chromatin activities can trigger severe metabolic
disease.

## Key facts

- **NIH application ID:** 10459503
- **Project number:** 5R01GM115879-08
- **Recipient organization:** UNIVERSITY OF TEXAS AT AUSTIN
- **Principal Investigator:** Hong Qiao
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $334,989
- **Award type:** 5
- **Project period:** 2015-08-01 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10459503

## Citation

> US National Institutes of Health, RePORTER application 10459503, Investigate the molecular mechanisms of the interplay between cell metabolism and histone modification in ethylene signaling in Arabadopsis (5R01GM115879-08). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10459503. Licensed CC0.

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