In our publication (Oh KS et al. 2018 Journal of Immunology), we uncovered an unexpected role of Ikaros, a protein which is known to promote immune cell development away from the myeloid (phagocytic) lineage. Not only is the protein expressed in phagocytic (pathogen-engulfing) cells, but it also regulates the expression of critical genes that are required to fight off infectious agents. Our study sheds a new light on the biological importance of Ikaros in a new cellular context, myeloid cells, and suggests that pharmacological inhibition of Ikaros with available compounds will modulate inflammatory responses in phagocytic cells of the immune system. In another subproject, we aimed to improve the genomic TF footprinting protocol to address the difficulty of capturing highly dynamic interactions of some TFs with target DNA elements in chromatin. The additional step which we introduced in the protocol can be easily incorporated by any laboratory. We have performed the modified assays and generated a panel of sequencing libraries to systematically assess how the various protocols affect the genomic footprints of dynamic proteins. The enrichment, complexity, and quality of each library was confirmed, and all the libraries were subject to ultra-deep Illumina paired-end read sequencing. The resulting dataset represents an unprecedented-scale resource data for the epigenetics and immunology communities, in addition to providing an insight on the effects of various crosslinking protocols (Oh KS et al. manuscript in preparation). Tissue-resident macrophages play a major role in tissue homeostasis. They have also been associated with age-related pathological inflammation. It is important to understand how macrophages are epigenetically and functionally altered during aging and in age-dependent chronic inflammation. To address this, we expanded our efforts to tissue-resident macrophages including peritoneal, and brain-resident macrophages. We performed ChIP-seq of a few histone marks, ATAC-seq, and RNA-seq using macrophages (BMDM) from young and aged mice (NIA aged colony at Charles River Lab) treated with lipopolysaccharide (LPS) for 0, 3, 8 hours. The analysis of these data is ongoing and so far has revealed intriguing age-related differential basal gene expression and responses to an inflammatory stimulus.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Investigator-Initiated Intramural Research Projects (ZIA)
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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