The spatial organization of genes in the interphase nucleus plays an important role in establishment and regulation of gene expression. However, little is known about genomic features of associating loci and how they relate to rapid transcriptional regulation by an inducible transcription factor. We combined genome-wide interaction profiling with expression, protein occupancy, and chromatin accessibility profiles, to investigate the properties of genomic loci that are in close proximity. We find that the nucleus is non-randomly organized in a conformation that correlates with gene expression. These hubs are enriched for specific transcription factors binding sites, and DNaseI hypersensitive sites. These findings indicate that chromosomal segments containing specific regulatory elements and open chromatin are arranged in nuclear domains that are poised to respond to diverse signals in general, and permit efficient gene regulation.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIABC010027-19
Application #
8763055
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
19
Fiscal Year
2013
Total Cost
$683,097
Indirect Cost
Name
National Cancer Institute Division of Basic Sciences
Department
Type
DUNS #
City
State
Country
Zip Code
Nakahashi, Hirotaka; Kwon, Kyong-Rim Kieffer; Resch, Wolfgang et al. (2013) A genome-wide map of CTCF multivalency redefines the CTCF code. Cell Rep 3:1678-89
Miranda, Tina B; Voss, Ty C; Hager, Gordon L (2013) High-throughput fluorescence-based screen to identify factors involved in nuclear receptor recruitment to response elements. Methods Mol Biol 1042:3-12
Hakim, Ofir; Sung, Myong-Hee; Nakayamada, Shingo et al. (2013) Spatial congregation of STAT binding directs selective nuclear architecture during T-cell functional differentiation. Genome Res 23:462-72
Voss, Ty C; Schiltz, R Louis; Sung, Myong-Hee et al. (2009) Combinatorial probabilistic chromatin interactions produce transcriptional heterogeneity. J Cell Sci 122:345-56
George, Anuja A; Schiltz, R Louis; Hager, Gordon L (2009) Dynamic access of the glucocorticoid receptor to response elements in chromatin. Int J Biochem Cell Biol 41:214-24
Voss, Ty C; Hager, Gordon L (2008) Visualizing chromatin dynamics in intact cells. Biochim Biophys Acta 1783:2044-51