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 acitivity 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 funciton at almost all regulatory elements in the murine genome.

National Institute of Health (NIH)
National Cancer Institute (NCI)
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National Cancer Institute Division of Basic Sciences
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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
Morris, Stephanie A; Baek, Songjoon; Sung, Myong-Hee et al. (2014) Overlapping chromatin-remodeling systems collaborate genome wide at dynamic chromatin transitions. Nat Struct Mol Biol 21:73-81
Miranda, Tina B; Morris, Stephanie A; Hager, Gordon L (2013) Complex genomic interactions in the dynamic regulation of transcription by the glucocorticoid receptor. Mol Cell Endocrinol 380:16-24
Stavreva, Diana A; Varticovski, Lyuba; Hager, Gordon L (2012) Complex dynamics of transcription regulation. Biochim Biophys Acta 1819:657-66
Romero, Octavio A; Setien, Fernando; John, Sam et al. (2012) The tumour suppressor and chromatin-remodelling factor BRG1 antagonizes Myc activity and promotes cell differentiation in human cancer. EMBO Mol Med 4:603-16
Hager, Gordon L; Varticovski, Lyuba (2012) Chromatin in time and space. Biochim Biophys Acta 1819:631
Wiench, Malgorzata; Miranda, Tina B; Hager, Gordon L (2011) Control of nuclear receptor function by local chromatin structure. FEBS J 278:2211-30
Wiench, Malgorzata; Hager, Gordon L (2010) Expanding horizons for nuclear receptors. EMBO Rep 11:569-71