Although glucocorticoids are widely used anti-inflammatory drugs, relevant mechanisms are unclear. In the study Oh KS et al., we monitored the epigenomic landscape of macrophages, and found that the gene-inducing activity of GR is crucial for boosting inhibitors of inflammatory factors. This cautions the idea that GR ligands selectively promoting trans-repression should improve therapeutic outcome. The 3D folding of a mammalian genome is cell-type specific and an important layer of gene regulation. In Portuguez AS et al, we report spatial clustering of adipogenic genes in cells undergoing adipogenesis. The results suggest stage-specific re-organization of genome architecture influenced by transcription factors which contribute to the establishment of the genetic program in mature fat cells. Nuclear architecture is largely non-random and is the product of many synergistic influences. In Sawyer IS et al., we propose that Cajal bodies contribute to the 3D structural organization of the nucleus by physically clustering target snRNA genes. In turn, this regulates spliceosomal component levels and shapes the transcriptome by regulating RNA splicing fidelity.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIAAG000390-02
Application #
9551859
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
2017
Total Cost
Indirect Cost
Name
Aging
Department
Type
DUNS #
City
State
Country
Zip Code
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
Sarusi Portuguez, Avital; Schwartz, Michal; Siersbaek, Rasmus et al. (2017) Hierarchical role for transcription factors and chromatin structure in genome organization along adipogenesis. FEBS J 284:3230-3244
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
Sawyer, Iain A; Sturgill, David; Sung, Myong-Hee et al. (2016) Cajal body function in genome organization and transcriptome diversity. Bioessays 38:1197-1208
Wang, Qiuyan; Sawyer, Iain A; Sung, Myong-Hee et al. (2016) Cajal bodies are linked to genome conformation. Nat Commun 7:10966
Sung, Myong-Hee; Baek, Songjoon; Hager, Gordon L (2016) Genome-wide footprinting: ready for prime time? Nat Methods 13:222-228
Baek, Songjoon; Sung, Myong-Hee (2016) Genome-Scale Analysis of Cell-Specific Regulatory Codes Using Nuclear Enzymes. Methods Mol Biol 1418:225-40
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