1) Using ChIP-Chip and ChIP-Seq methodologies, we characterized transcription factor regulatory elements throughout the murine and human genomes. While many transcription factor binding sites are found in the immediate vicinity of target promoters, a large set of transcription factor interaction sites are located at great distances from any promoter element. 2) We have characterized the chromatin landscape at local transcription factor interaction events. We find that transcription factor binding to regulatory elements usually results in local chromatin transitions identified as DNaseI hypersensitive sites (DHSs). While transcription factors can bind to unremodeled nucleosomes in vitro, we report that transcription factor interactions with the chromatin fiber always leads to the local reorganization of nucleosomes, indicating the chromatin remodeling is a universal feature of transcription factor template binding. 3) Transcription factor induced chromatin remodeling in model systems has been correlated with ATP-dependent chromatin remodeler action. Transcription factors frequently interact at sites already hypersensitive to DNaseI attack. Thus transcription factors can mobilize remodeling systems and interact either at pre-existing sites of chromatin remodeling or newly created sites. There are four types of transcription factor chromatin interactions: factor-dependent sites are called de novo events;factor-independent events are designated pre-programmed sites and reliy on other factors;each of these groups in turn comprise subsets requiring the action of differnent remodeling proteins. 4) The local organization of the factor chromatin interaction sites is highly cell specific, and strongly correlated with the transcriptional response. Factor sites linked to promoters that are non-responsive in a given cell type are refractory to factor directed remodeling, and resistant to factor binding. This leads to the hypothesis that local chromatin structural organization in a given cell type is a major determinant of tissue specific factor action. 5) Integration of these cancepts led to the development of a new paradigm for transcription factor interaction with chromatin, termed """"""""assisted loading.""""""""

National Institute of Health (NIH)
National Cancer Institute (NCI)
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
Application #
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
National Cancer Institute Division of Basic Sciences
Zip Code
Thompson, Bethtrice; Varticovski, Lyuba; Baek, Songjoon et al. (2016) Genome-Wide Chromatin Landscape Transitions Identify Novel Pathways in Early Commitment to Osteoblast Differentiation. PLoS One 11:e0148619
Swinstead, Erin E; Miranda, Tina B; Paakinaho, Ville et al. (2016) Steroid Receptors Reprogram FoxA1 Occupancy through Dynamic Chromatin Transitions. Cell 165:593-605
Tesikova, Martina; Dezitter, Xavier; Nenseth, Hatice Z et al. (2016) Divergent Binding and Transactivation by Two Related Steroid Receptors at the Same Response Element. J Biol Chem 291:11899-910
Sung, Myong-Hee; Baek, Songjoon; Hager, Gordon L (2016) Genome-wide footprinting: ready for prime time? Nat Methods 13:222-8
Goldstein, Ido; Hager, Gordon L (2015) Transcriptional and Chromatin Regulation during Fasting - The Genomic Era. Trends Endocrinol Metab 26:699-710
Grøntved, Lars; Waterfall, Joshua J; Kim, Dong Wook et al. (2015) Transcriptional activation by the thyroid hormone receptor through ligand-dependent receptor recruitment and chromatin remodelling. Nat Commun 6:7048
Hsiung, Chris C-S; Morrissey, Christapher S; Udugama, Maheshi et al. (2015) Genome accessibility is widely preserved and locally modulated during mitosis. Genome Res 25:213-25
Siersbaek, Rasmus; Baek, Songjoon; Rabiee, Atefeh et al. (2014) Molecular architecture of transcription factor hotspots in early adipogenesis. Cell Rep 7:1434-42
Voss, Ty C; Hager, Gordon L (2014) Dynamic regulation of transcriptional states by chromatin and transcription factors. Nat Rev Genet 15:69-81
Sung, Myong-Hee; Guertin, Michael J; Baek, Songjoon et al. (2014) DNase footprint signatures are dictated by factor dynamics and DNA sequence. Mol Cell 56:275-85

Showing the most recent 10 out of 47 publications