Mechanisms of the interplay between metabolism, chromatin regulation, and transcriptional control in ethylene signaling and stress responses in Arabidopsis

Nuclear enzymes, chromatin, and chromatin modifications collectively enable cells and organisms to respond and survive in dynamic environments. Chromatin modifying enzymes play central roles in this process by utilizing cofactors derived from cellular metabolism to exert their catalytic activities. Consequently, the metabolic status of the cell can influence histone modifications and the structure, density and location of nucleosomes, thereby shaping epigenetic landscapes and gene expression programs. Mitochondria play a crucial role in cellular stress response by signaling to the nucleus through changes in metabolic state. Therefore, elucidating how mitochondria and nucleus coordinate to regulate metabolism and chromatin regulation to shape transcriptional regulation will reveal the fundamental processes that govern cellular stress responses and adaptation. Metabolic stress and hormone signaling often converge to reprogram chromatin to prioritize genes for survival, growth, or stress responses. The plant hormone ethylene signaling pathway in Arabidopsis serves as an ideal model for this research, as it integrates hormonal and stress signals to mediate plant growth, development, and responses to environmental challenges such as hypoxia, pathogen infection, and water deficiency. We have discovered that EIN2, an essential ethylene signaling factor, is also a key component of the histone modification that directly regulates H3K14Ac and H3K23Ac to mediate the transcriptional reprogramming in response to ethylene, which establishes a direct link between ethylene signaling and chromatin regulation. Additionally, we have found that alterations in the chromatin architecture in ein2-5, the ethylene insensitive mutant, prevent ethylene-induced transcriptional reprogramming. Furthermore, our latest findings provide compelling evidence showing that the PYRUVATE DEHYDROGENASE COMPLEX (PDC), the acetyl-donor of histone acetylation, can translocate from the mitochondria to the nucleus to provide acetyl CoA for histone acetylation regulation over ethylene- regulated genes. Standing on our recent groundbreaking work, we will continue to investigate how mitochondrial- nuclear coordination modulates metabolism and chromatin regulation to control transcriptional reprogramming in ethylene signaling and stress responses in three directions from three directions: (1) Elucidating pathways and the mechanisms by which ethylene signals are transmitted from the ER to nuclear chromatin for shaping cellular responses; (2) Investigating chromatin dynamics and transcriptional control mechanisms in ethylene response; (3) Integrative study of mitochondrial-nuclear communication governing metabolism and chromatin regulation in plant ethylene and stress responses. Our overarching goal is to uncover how mitochondrial-nuclear coordination modulates metabolism and chromatin regulation, ultimately controlling transcriptional responses to plant hormone and stresses. This research will provide key insights into the molecular mechanisms that govern how metabolism and chromatin interplay to drive cellular responses to stress and disease, enhancing our understanding of cellular resilience and homeostasis. Project Number: 1R35GM161337-01 | Fiscal Year: 2026 | NIH Institute/Center: National Institute of General Medical Sciences (NIGMS) | Principal Investigator: Hong Qiao | Institution: UNIVERSITY OF TEXAS AT AUSTIN, AUSTIN, TX | Award Amount: $429,650 | Activity Code: R35 | Study Section: Maximizing Investigators' Research Award C Study Section[MRAC] View on NIH RePORTER: https://reporter.nih.gov/project-details/11259632