The importance of histone acetylation in numerous cellular processes is becoming increasingly clear. Recent findings have implicated it in the establishment of apical-basal polarity in developing plant embryos. The affects of histone acetylation on gene regulation during embryogenesis have not been well studied because loss of proteins involve in this process usually lead to early embryonic lethality. This is not the case in Arabidopsis, making it an ideal model organism for studying the role of histone acetylation in development. The Arabidopsis protein HAG1, a GCN5-like histone acetyltransferase, is involved in maintaining the axis of polarity, but the mechanism by which it acts is unknown. Mutation of TPL, a transcriptional co-repressor, can lead to full homeotic conversion of the apical shoot into a second basal root, a process that requires HAG1. This proposal aims to clarify the role of HAG1 in this conversion as well as in normal embryonic development through both global and local studies and explore the possibility of its involvement in establishing an epigenetic code that regulates pattern formation. Genome-wide microarray and chromatin immunoprecipitation experiments will be used to identify genes directly regulated by HAG1 during embryogenesis. To understand the mechanism of this regulation, histone acetylation patterns in the promoter regions of HAG1-dependent genes will be determined. A screen for suppressors and enhancers of the hag1-3 mutant allele will also be performed, which will identify the broader transcriptional regulatory network in which HAG1 functions and the relationship of HAG1-dependent regulation to other known pathways that control apical/basal polarity. The overall goal is to understand HAGI'scontribution to apical- basal polarity in embryos and discover new players in this critical process, findings that are likely to be relevant for animals as well as plants. This is particularly important in regards to human health, as both birth defects and some forms of cancer are developmental in origin. Furthermore, recent work has implicated mis-regulation of acetylation with numerous human diseases. Relevance Understanding how different cell types arise from a single cell is fundamental to public health as this process is critical for development, and disruption of it leads to various diseases, including cancer. This proposal aims to explore one aspect of this process, histone acetylation, a phenomenon that has been linked to development, as well as many human pathologies such as neurodegenerative diseases, cancer and asthma. The findingsfrom this study will aid in understanding this important process.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Postdoctoral Individual National Research Service Award (F32)
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Special Emphasis Panel (ZRG1-F08-G (20))
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Bender, Michael T
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Salk Institute for Biological Studies
La Jolla
United States
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