Transcription Systems Dynamics and Biology Unit
Myong-Hee Sung, PhD, Chief
The long-term goal of the Transcription Systems Dynamics and Biology Unit (TSDBU) is to understand how transcriptional regulators control gene expression in immune processes and during aging. We apply imaging, mathematical, biochemical, and molecular biological approaches to understand the mechanisms of transcription factor signaling and functional genome regulation. Single cell approaches using fluorescent microscopy and mathematical modeling are necessary to decipher how transcription factors interpret information encoded in signaling dynamics and transmit the contextual information to downstream gene regulation. On another front of systems biology, recent breakthroughs in genomic tools have greatly expanded our ability to investigate chromatin characteristics that correspond to cell state-specific genome regulation. The TSDBU will utilize epigenomic analysis methods to characterize the chromatin landscapes resulting from dynamic actions of transcription factors. This research direction is aimed at elucidation of chromatin features which change with age and contribute to the aging process, one of the hallmarks of aging (Lopez-Otin et al., 2013). It is anticipated that utilizing these two analysis frameworks (one top-down, the other bottom-up) will provide unprecedented insight into the systems basis of how genome regulation is altered in autoimmune diseases, inflammatory malignancies, neurodegeneration, and aging. The TSDBU led by a Stadtman Investigator Mia Sung developed fluorescent knock-in mice that track one or both of the canonical subunits of NF-κB. The power of these reporters is illustrated in Rahman et al. (Cell Reports, 2022) with several approaches that gain deeper insights to NF-κB biology. The mice enable diverse applications from single-molecule analyses to in situ identification of active inflammatory cells.
- Systems Biology
- Computational Biology
- Genetics and Genomics
- Cell Biology
- Chromosome Biology
Findings and Publications
Martin, Erik W., Pacholewska, Alicja, Patel, Heta, Dashora, Himanshu, Sung, Myong-Hee. Integrative analysis suggests cell type–specific decoding of NF-κB dynamicsScience Signaling, February 2020 DOI: 10.1126/scisignal.aax7195
Sung, M.H., Baek, S., Hager, G.L. Genome-wide footprinting: ready for prime time? Nat Methods. 2016 Feb 25;13(3):222-8. doi: 10.1038/nmeth.3766.
Sung, M.H., Guertin M., Baek S., Hager G.L. DNase footprint signatures are dictated by factor dynamics and DNA sequence. Mol Cell 2014, 56(2): 275-85.
Sung, M.H., Li, N., Lao, Q., Gottschalk, R., Hager, G.L., Fraser ID: Switching of the relative dominance between feedback mechanisms in LPS-induced NF-κB signaling. Science Signaling 2014, 7(308) ra6.
Sung, M.H., Salvatore, L., De Lorenzi, R., Indrawan, A., Pasparakis, M., Hager, G.L., Bianchi, M.E., Agresti, A.: Sustained oscillations of NF-κB produce distinct genome scanning and gene expression profiles. PLoS One 2009, 4: e7163