Our long-term goal of this exploratory research proposal is to determine how chromosome conformation and subnuclear position affect the host response to viruses. Significance and role of large-scale nuclear processes of folding and juxtaposition of chromosomal fibers during innate immune response to viruses remain relatively unknown. However, these processes represent unexplored epigenetic targets for modulating the innate immune system for potential therapies. To understand these nuclear processes involved in anti-viral response in human cells, we will characterize the molecular mechanisms that modulate chromosomal conformation and subnuclear location of the type I interferon locus in the genome of diploid fibroblasts and lymphoblasts during viral infection. A better understanding of the regulatory mechanisms involved in the production of type I interferons is fundamental to the development of therapeutic strategies for treating viral infections and inflammatory diseases such as autoimmunity.
The type I interferons are critical component of the innate immune response to microbial pathogens, and they coordinate integration of innate and adaptive immune responses. Our project aims to uncover epigenetic mechanisms involving chromosome folding that mediate dynamic and precise activation of type I interferon locus in human cells. These studies will yield potential targets that can be modulated for anti-viral therapies.
|Kim, Yoon Jung; Xie, Peng; Cao, Lian et al. (2018) Global transcriptional activity dynamics reveal functional enhancer RNAs. Genome Res 28:1799-1811|
|Johnson, Brian S; Zhao, Ying-Tao; Fasolino, Maria et al. (2017) Biotin tagging of MeCP2 in mice reveals contextual insights into the Rett syndrome transcriptome. Nat Med 23:1203-1214|
|Tan, Justin L; Fogley, Rachel D; Flynn, Ryan A et al. (2016) Stress from Nucleotide Depletion Activates the Transcriptional Regulator HEXIM1 to Suppress Melanoma. Mol Cell 62:34-46|
|Cha, Boksik; Geng, Xin; Mahamud, Md Riaj et al. (2016) Mechanotransduction activates canonical Wnt/?-catenin signaling to promote lymphatic vascular patterning and the development of lymphatic and lymphovenous valves. Genes Dev 30:1454-69|
|Nwigwe, Ifeoma Jane; Kim, Yoon Jung; Wacker, David A et al. (2015) Boundary Associated Long Noncoding RNA Mediates Long-Range Chromosomal Interactions. PLoS One 10:e0136104|
|Greer, Celeste B; Tanaka, Yoshiaki; Kim, Yoon Jung et al. (2015) Histone Deacetylases Positively Regulate Transcription through the Elongation Machinery. Cell Rep 13:1444-1455|
|Banerjee, A Raja; Kim, Yoon Jung; Kim, Tae Hoon (2014) A novel virus-inducible enhancer of the interferon-? gene with tightly linked promoter and enhancer activities. Nucleic Acids Res 42:12537-54|
|Kim, Lark Kyun; Esplugues, Enric; Zorca, Cornelia E et al. (2014) Oct-1 regulates IL-17 expression by directing interchromosomal associations in conjunction with CTCF in T cells. Mol Cell 54:56-66|