The goal of the proposed research is to better understand the mechanism(s) by which the Polycomb Group (PcG) of proteins mediate gene silencing. This work is significant from a human health perspective because it has the potential to illuminate the mechanism of how PcG proteins participate in cancer and stem cell biology. According to current models of PcG-mediated gene silencing, the methylation of histone H3 by the EZH2 complex serves to recruit the PRC-1 complex as a result of specific interactions between the Polycomb protein (Pc) and methyl H3 lysine 27. While a specific interaction between PC and methylated peptides has been shown, an interaction with methyl K27 in a physiologically relevant context has not been demonstrated. To test the model, specific aim 1 is to address the possibility that PC interacts specifically with methyl H3 K27 in the context of nucleosomes. In the second step of PcG silencing, again according to current models, the ubiquitylation of H2A by the recruited PRC-1 complex leads to the inhibition of transcription.
Specific aim 2 is to test this model by establishing an in vitro silencing system that depends on H2A ubiquitylation. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32GM075577-02
Application #
7235303
Study Section
Special Emphasis Panel (ZRG1-F08-G (20))
Program Officer
Dearolf, Charles R
Project Start
2006-04-01
Project End
2007-06-30
Budget Start
2007-04-01
Budget End
2007-06-30
Support Year
2
Fiscal Year
2007
Total Cost
$14,357
Indirect Cost
Name
University of North Carolina Chapel Hill
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
608195277
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599