Abstract

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.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIABC010027-18
Application #
8552642
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
18
Fiscal Year
2012
Total Cost
$332,833
Indirect Cost

  Institution

Name
National Cancer Institute Division of Basic Sciences
Department
Type
DUNS #
City
State
Country
Zip Code

  Publications

Oh, Kyu-Seon; Gottschalk, Rachel A; Lounsbury, Nicolas W et al. (2018) Dual Roles for Ikaros in Regulation of Macrophage Chromatin State and Inflammatory Gene Expression. J Immunol 201:757-771
Presman, Diego M; Ball, David A; Paakinaho, Ville et al. (2017) Quantifying transcription factor binding dynamics at the single-molecule level in live cells. Methods 123:76-88
Oh, Kyu-Seon; Patel, Heta; Gottschalk, Rachel A et al. (2017) Anti-Inflammatory Chromatinscape Suggests Alternative Mechanisms of Glucocorticoid Receptor Action. Immunity 47:298-309.e5
Stavreva, Diana A; Varticovski, Lyuba; Levkova, Ludmila et al. (2016) Novel cell-based assay for detection of thyroid receptor beta-interacting environmental contaminants. Toxicology 368-369:69-79
Stavreva, Diana A; Hager, Gordon L (2015) Chromatin structure and gene regulation: a dynamic view of enhancer function. Nucleus 6:442-8
Dull, Angie B; George, Anuja A; Goncharova, Ekaterina I et al. (2014) Identification of compounds by high-content screening that induce cytoplasmic to nuclear localization of a fluorescent estrogen receptor ? chimera and exhibit agonist or antagonist activity in vitro. J Biomol Screen 19:242-52
Guertin, Michael J; Zhang, Xuesen; Coonrod, Scott A et al. (2014) Transient estrogen receptor binding and p300 redistribution support a squelching mechanism for estradiol-repressed genes. Mol Endocrinol 28:1522-33
Aguilar-Arnal, Lorena; Hakim, Ofir; Patel, Vishal R et al. (2013) Cycles in spatial and temporal chromosomal organization driven by the circadian clock. Nat Struct Mol Biol 20:1206-13
Kieffer-Kwon, Kyong-Rim; Tang, Zhonghui; Mathe, Ewy et al. (2013) Interactome maps of mouse gene regulatory domains reveal basic principles of transcriptional regulation. Cell 155:1507-20
Nakahashi, Hirotaka; Kieffer Kwon, Kyong-Rim; Resch, Wolfgang et al. (2013) A genome-wide map of CTCF multivalency redefines the CTCF code. Cell Rep 3:1678-1689

Showing the most recent 10 out of 27 publications