Philip A. Cole, M.D., Ph.D.
Chemical Activity Probes for Identification of Novel Acetyltransferases
This core technology involves the use of chemical affinity labeling reagents to discover and characterize novel histone acetyltransferase (HAT) enzymes. It is hypothesized here that families of HATs remain to be discovered, in part due to the limited approaches that have been so far employed for HAT identification. By applying active site labeling agents, it should be possible to find new HAT enzymes which can open new vistas in our understanding of gene regulation.
We have three specific aims:
- Specific Aim 1. Synthesize a series of chemically reactive CoA analogs for affinity labeling studies.
- Specific Aim 2. Evaluate the CoA affinity reagents with known, purified HATs, and spiked HATs in mixtures and immobilized in microarrays.
- Specific Aim 3. Identify and characterize novel CoA-crosslinked proteins as potential HATs.
In addition to these aims, a fourth aim to find related lysine demethylases using activity probes will also be pursued.
These projects will be carried out in close consultation and collaboration with our TCNP coinvestigators: Heng Zhu, Bob Cotter, Akhilesh Pandey, Paddy Onyango, Shelley Berger, and Jorge Escalante.