The function of the nucleus is to maintain the integrity of genes and to control the activities of the cell by regulating gene expression. Nuclear enzymes, chromatin and its modifications contribute to the abilities of cells and organisms to respond and survive in dynamic environments. Dysfunctions nuclear processes contribute directly to cancer progression and genetic disorders. We are using Arabidopsis to study early nuclear events in ethylene signaling, which is important not only in plant growth and development, but also in various responses to stresses such as drought, flooding, and infection. Our long-term goal is to develop a validated mechanistic model that accurately describes how chromatin regulators receive signals and how the regulation is established in the first place in ethylene signaling. In the ethylene signaling pathway, EIN2 is the essential key regulator, and it is the only gene whose null mutant renders completely ethylene insensitive. Our recent studies have revealed that EIN2 mediates transmission of ethylene signaling that originates at the endoplasmic reticulum membrane to the nucleus and that the EIN2 C-terminus is cleaved and translocated to the nucleus to initiate the ethylene response. However, the molecular mechanism that nuclear translocation of EIN2, the function of EIN2 C-terminal end in the nucleus and how EIN2 C-terminal end communicate with EIN3 are not understood. Through extensive yeast two-hybrid screening and immunoprecipitation followed by mass spectrometry assay, we identified a strong EIN2 C-terminus interactor. This protein is localized to the nucleus, and strikingly, it is associated with histones and involved in the regulation of histone modifications. Our preliminary data strongly indicate that the EIN2 C-terminus participates in histone modification, providing a link between signaling and chromatin regulation. This proposal has the following specific aims: (1) Determine the function of EIN2 C-terminus and identify and characterize functions of other components involved in the early nuclear response to ethylene signaling; (2) Uncover the mechanism that how chromatin regulators receive ethylene signaling to regulate the initiation of the specific transcriptional regulation. The molecular mechanisms under investigation involve chromatin regulation and transcriptional reprogramming, which are shared in general in both plants and animals; (3) Elucidate the molecular mechanisms by which EIN2 C-terminal is translocated to the nucleus in response to ethylene.

Public Health Relevance

Signaling systems regulate the cell events responsible for survival, development and homeostasis. Malfunction of signaling circuits causes many diseases, such as cancer. Nuclear enzymes, chromatin and its modifications contribute to the abilities of cells and organisms to respond and survive in dynamic environments. Dysfunctions nuclear processes contribute directly to cancer progression and genetic disorders. The research proposed here to study the communication between signaling and chromatin regulation has the potential to provide an important basis to the effort of developing novel strategies for finding ne drugs.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM115879-05
Application #
9690158
Study Section
Cellular Signaling and Regulatory Systems Study Section (CSRS)
Program Officer
Carter, Anthony D
Project Start
2015-08-01
Project End
2020-04-30
Budget Start
2019-05-01
Budget End
2020-04-30
Support Year
5
Fiscal Year
2019
Total Cost
Indirect Cost
Name
University of Texas Austin
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
170230239
City
Austin
State
TX
Country
United States
Zip Code
78759
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Zhang, Fan; Wang, Likai; Ko, Eun Esther et al. (2018) Histone Deacetylases SRT1 and SRT2 Interact with ENAP1 to Mediate Ethylene-Induced Transcriptional Repression. Plant Cell 30:153-166
Song, Qingxin; Ando, Atsumi; Xu, Dongqing et al. (2018) Diurnal down-regulation of ethylene biosynthesis mediates biomass heterosis. Proc Natl Acad Sci U S A 115:5606-5611
Wang, Likai; Zhang, Fan; Rode, Siddharth et al. (2017) Ethylene induces combinatorial effects of histone H3 acetylation in gene expression in Arabidopsis. BMC Genomics 18:538
Zhang, Fan; Wang, Likai; Qi, Bin et al. (2017) EIN2 mediates direct regulation of histone acetylation in the ethylene response. Proc Natl Acad Sci U S A 114:10274-10279
Zhang, Fan; Qi, Bin; Wang, Likai et al. (2016) EIN2-dependent regulation of acetylation of histone H3K14 and non-canonical histone H3K23 in ethylene signalling. Nat Commun 7:13018
Zhang, Fan; Wang, Likai; Lim, Jae Yun et al. (2016) Phosphorylation of CBP20 Links MicroRNA to Root Growth in the Ethylene Response. PLoS Genet 12:e1006437