Super-enhancers and methods of use thereof

摘要

The present invention relates in some aspects to super-enhancers and related compositions, methods, and agents that are useful for modulating expression of cell type-specific genes that are required for maintenance of cell identity (e.g., embryonic stem cell identity) or maintenance of a disease state (e.g., cancer).

主权项

1. A method of identifying a super-enhancer in a sample comprising chromatin, comprising: obtaining chromatin from a cell wherein said chromatin has been cross-linked such that chromosomal nucleic acid in the chromatin is cross-linked to a component selected from the group consisting of BRD4, a Mediator component and H3K27Ac with which the chromosomal nucleic acid is associated to form a cross-linked complex; contacting said cross-linked complex with a ligand having affinity for the component, said ligand selected from the group consisting of an antibody to BRD4, an antibody to a Mediator component, and an antibody to H3K27Ac, to form a complex between the cross-linked complex and the ligand;
determining an amount of ligand bound to each enhancer in the cross-linked complex in the cell; and utilizing the determined amount of ligand bound to each enhancer to identify a super-enhancer, wherein the identified super-enhancer is bound to at least 10-fold more ligand than the median amount of ligand bound to enhancer within the cell.