Methods and compositions for targeting prc2 gene targets
AssigneeThe Johns Hopkins University
InventorsAndrew P. Feinberg, Michael A. Koldobskiy, Oscar Camacho
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Abstract
The invention provides herein epigenomic changes identified in old mice compared to young mice or old mice treated with Oct4, Sox2, Klf4 and c-Myc (OSKM). The invention further provides methods of identifying a compound by analyzing one or more PRC2-associated epigenomic change in a sample before and after contacting the sample with one or more compounds. Also provided herein are methods of using compounds identified using the methods described herein for improving proliferative capacity, cell and tissue regeneration, and/or reducing fibrosis.
Claims13
A method of identifying a compound comprising:
- analyzing a PRC2-associated epigenomic change in a sample before and after contacting the sample with the compound,
- wherein the PRC2-associated epigenomic change comprises a decrease in mean methylation level (MML) or a reduction in normalized methylation entropy (NME) in one or more PRC2 gene targets in the sample after contacting with the compound.
A method of identifying a genomic region of differential DNA methylation comprising:
- a) obtaining a DNA sample from one or more of a young cohort, an old cohort and an Oct4, Sox2, Klf4 and c-Myc (OSKM) treated old cohort;
- b) performing whole-genome bisulfite sequencing (WGBS) on the DNA sample;
- c) calculating DNA methylation potential energy landscape across the genome of the DNA sample;
- d) measuring a mean methylation level (MML) and a normalized methylation entropy (NME) in an analysis region of the DNA sample;
- and
- e) identifying the genomic region of differential DNA methylation in the young cohort and the OSKM treated old cohort as compared to the DNA sample from the old cohort.
Dependencies are inferred from the claim text.