With genome sequence data available in massive abundance, the architecture of the mammalian genome, and the individual variation governing our traits are becoming increasingly understood. The technologies that have produced our sequence data are now being applied to characterize the structure and variation within our epigenome. Epigenetic modifications, which include DNA methylation and a variety of covalent changes to histone tails, are emerging as master regulators that control how sequence information within our genome is utilized. Proper placement and removal of epigenetic marks is essential for normal development, and misplacement of these marks are initiating events for many disease states. A host of enzymes and cofactors that place modifications in the epigenome are known, but almost nothing is known about how they select genomic locations to modify. Understanding how epigenetic states are established and maintained is of fundamental importance to human biology. My lab has identified a naturally occurring DNA sequence that has DNA methylation promoter activity: It is both necessary and sufficient to direct the placement of local DNA methylation in mice. No other naturally occurring sequence with this activity has been identified. Just as the dissection of transcriptional promoters facilitated the discovery of transcription mechanisms, the DNA methylation promoter we've discovered provides a unique opportunity for elaborating the mechanisms governing placement of this essential epigenetic mark. There are four prominent sequence features within the DNA methylation promoter hypothesized to be important for its function. The four Aims proposed here will reveal their roles in promoting DNA methylation.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA098597-09
Application #
8109829
Study Section
Molecular Genetics B Study Section (MGB)
Program Officer
Okano, Paul
Project Start
2003-02-25
Project End
2012-07-31
Budget Start
2011-08-01
Budget End
2012-07-31
Support Year
9
Fiscal Year
2011
Total Cost
$283,822
Indirect Cost
Name
Cornell University
Department
Nutrition
Type
Schools of Earth Sciences/Natur
DUNS #
872612445
City
Ithaca
State
NY
Country
United States
Zip Code
14850
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