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.
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.
