Epigenetic modification is an important gene regulatory mechanism and plays quintessential roles in the control of genome integrity, development, environmental responses, and diseases. Despite the large amount of studies describing altered modification patterns in abnormal developmental and pathological tissues, whether they are a cause or a consequence is poorly understood. This proposal dissects molecular mechanism of epigenetic regulation and functional consequences of altered epigenetic patterns under physiological conditions. Specifically, we investigate 1) how chromatin senses and memorizes the environmental stimuli; 2) how an epigenetic switch regulates developmental phase transition; and 3) how epigenetic modification safeguards the genome integrity. We use the flowering plant Arabidopsis, proved to be a robust system for mechanistic epigenetic studies, as our model system. Arabidopsis shares with mammals the common core cytosine DNA methylation machinery that is lacking in other model organisms (e.g. Saccharomyces cerevisiae, Caenorhabditis elegans, and Drosophila melanogaster). Importantly, Arabidopsis tolerates null mutations in most epigenetic regulators that are often lethal in animals, providing a significant advantage to investigate in-depth mechanisms under developmental and physiological conditions. As we probe basic principles governing epigenetic regulation that are conserved across eukaryotic organisms, knowledge acquired from our pioneering studies in Arabidopsis will help accelerate progress in deciphering the relevant mechanisms in human. In-depth mechanistic knowledge is crucial for understanding how epigenetic modification contributes to developmental defects and disease. Such knowledge will provide the necessary insight to develop new medicines that target the respective epigenetic processes.

Public Health Relevance

RELEVANCY STATEMENT / NARRATIVE Epigenetic modifications (the layer of chemical information sitting on top of the genome) that switch genes `on' or `off' play critical roles in many biological processes, including genome expression, genome integrity, development, and diseases. Its correct deposition is relevant for genome function and development, and is often disturbed in abnormal developmental and pathological tissues such as cancers. The proposed research programs are relevant to public health, because in-depth mechanistic epigenetic knowledge is crucial for understanding how epigenetic modification is coordinated with other critical developmental, physiological, and pathological processes. Such knowledge will provide the necessary insight to develop new medicines that target the corresponding epigenetic processes.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Unknown (R35)
Project #
5R35GM124806-03
Application #
9735387
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Carter, Anthony D
Project Start
2017-08-01
Project End
2022-07-31
Budget Start
2019-08-01
Budget End
2020-07-31
Support Year
3
Fiscal Year
2019
Total Cost
Indirect Cost
Name
University of Wisconsin Madison
Department
Genetics
Type
Earth Sciences/Resources
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715
Qian, Shuiming; Lv, Xinchen; Scheid, Ray N et al. (2018) Dual recognition of H3K4me3 and H3K27me3 by a plant histone reader SHL. Nat Commun 9:2425
Lu, Li; Chen, Xiangsong; Qian, Shuiming et al. (2018) The plant-specific histone residue Phe41 is important for genome-wide H3.1 distribution. Nat Commun 9:630
Chen, Xiangsong; Lu, Li; Qian, Shuiming et al. (2018) Canonical and Noncanonical Actions of Arabidopsis Histone Deacetylases in Ribosomal RNA Processing. Plant Cell 30:134-152