We discovered that the Brg1 chromatin remodeling protein is frequently mutated in human lung cancer. We showed that gene expression profiles are heavily disrupted in lung cells harboring these mutations, and further showed that restoration of wild type Brg1 function will partially restore normal expression profiles.We have developed dominant negative forms of the Brg1, INO80, Snf2h, and CHD4 human chromatin remodeling proteins, and have developed individual cell lines expressing these dominant negative activities under inducible (tetracycline) regulation. We have characterized the biochemical activity of these mutant complexes, and shown that they are each defective in nucleosome remodeling activity. We are studying the potential role of these remodeling systems in the action of nuclear receptors at specific sites of remodeling genome wide.We have discovered that multiple remodeling complexes function at almost all regulatory elements in the murine genome.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIABC010646-09
Application #
8552760
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
9
Fiscal Year
2012
Total Cost
$332,833
Indirect Cost
Name
National Cancer Institute Division of Basic Sciences
Department
Type
DUNS #
City
State
Country
Zip Code
Johnson, Thomas A; Chereji, Razvan V; Stavreva, Diana A et al. (2018) Conventional and pioneer modes of glucocorticoid receptor interaction with enhancer chromatin in vivo. Nucleic Acids Res 46:203-214
Salomon-Kent, Ronit; Marom, Ronit; John, Sam et al. (2015) New Face for Chromatin-Related Mesenchymal Modulator: n-CHD9 Localizes to Nucleoli and Interacts With Ribosomal Genes. J Cell Physiol 230:2270-80
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