• Molecules and Cells
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• v.24 no.3
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• pp.307-315
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• 2007

Gene regulation is a fundamental process in biological systems, where transcription factors (TFs) play crucial roles. Inferring transcriptional interactions between TFs and their target genes has utmost importance for understanding the complex regulatory mechanisms in cellular systems. On one hand, with the rapid progress of various high-throughput experiment techniques, more and more biological data become available, which makes it possible to quantitatively study gene regulation in a systematic manner. On the other hand, transcription regulation is a complex biological process mediated by many events such as post-translational modifications, degradation, and competitive binding of multiple TFs. In this review, with a particular emphasis on computational methods, we report the recent advances of the research topics related to transcriptional regulatory networks, including how to infer transcriptional interactions, reveal combinatorial regulation mechanisms, and reconstruct TF activity profiles.

• Biotechnology and Bioprocess Engineering:BBE
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• v.10 no.5
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• pp.385-399
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• 2005

The phenotypic response of a cell results from a well orchestrated web of complex interactions which propagate from the genetic architecture through the metabolic flux network. To rationally design cell factories which carry out specific functional objectives by controlling this hierarchical system is a challenge. Transcriptome analysis, the most mature high-throughput measurement technology, has been readily applied In strain improvement programs in an attempt to Identify genes involved in expressing a given phenotype. Unfortunately, while differentially expressed genes may provide targets for metabolic engineering, phenotypic responses are often not directly linked to transcriptional patterns, This limits the application of genome-wide transcriptional analysis for the design of cell factories. However, improved tools for integrating transcriptional data with other high-throughput measurements and known biological interactions are emerging. These tools hold significant promise for providing the framework to comprehensively dissect the regulatory mechanisms that identify the cellular control mechanisms and lead to more effective strategies to rewire the cellular control elements for metabolic engineering.

• Toxicological Research
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• v.22 no.1
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• pp.15-22
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• 2006

Many of endocrine disrupting chemicals induce effects via interaction with hormone receptors and responsive elements in target cells. We investigated endocrine disrupting effects of some food additives and contaminants including BHA, BHT, ethoxyquin, propionic acid, sorbic acid, benzoic acid, CPM, aflatoxin B1, cadmium chloride, genistein, TCDD and PCBs in yeast transformants expressing human steroid hormone receptors along with steroid responsive elements. The response limit of genetically recombinant yeast to $17{\beta}$-estradiol, testosterone and progesterone was $1{\times}10^{-16},\;1{\times}10^{-12}\;and\;1{\times}10^{-13}M$, respectively. BHT induced weak transcriptional activity in estrogen sensitive yeast, while BHA and sorbic acid interacted weakly with androgen receptor/responsive element. CPM induced transcriptional activities in all types of yeasts sensitive to steroid hormones. Zearalenone and genistein induced high transcriptional activation in estrogen sensitive yeast with relative potencies almost $10^8$ folds lower than $17{\beta}$-estradiol. TCDD induced transcriptional activation weakly in estrogen- and progesterone- sensitive yeasts. This study elucidated that recombinant yeast is a sensitive and high-throughput system and can be used for the direct assessment on chemical interactions with steroid receptors and responsive elements. Also, the present study raises the requirement of evaluation on the endocrine disrupting effects of BHT, BHA, sorbic acid, CPM and TCDD for their transcription activity in yeast screening system though weak in intensity.

• Proceedings of the Korean Magnetic Resonance Society Conference
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• 2002.08a
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• pp.87-87
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• 2002

• Journal of the Korean Magnetic Resonance Society
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• v.19 no.2
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• pp.61-66
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• 2015

The plant hormone auxin is involved in all stages of plant development. Aux/IAAs are the transcriptional repressors that bind to the Auxin Response Factors (ARFs) to regulate the gene expression upon auxin release. Aux/IAA have highly conserved C-terminal domains (domains III-IV) that mediate both homotypic and heterotypic interactions between Aux/IAA and ARF family proteins. Recent studies revealed that the conserved domains III-IV share a common ${\beta}$-grasp fold that oligomerizes in a front-to-back manner. In particular, Aux/IAA contains a mobile insert helix in the domain III-IV, whereas ARFs do not. Here, we investigated the dynamics of the insert helix using paramagnetic NMR spectroscopy. The insert helix exhibited fast motions in the ps-ns time scale from $^{15}N$ relaxation data, but the amplitude of the motion is likely limited to the local neighborhood. Our result suggests that the motion of the helix may have functional implications in protein-protein interactions for transcriptional regulations.

• BMB Reports
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• v.56 no.7
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• pp.398-403
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• 2023

Natural killer (NK) cells are an essential part of the innate immune system that helps control infections and tumors. Recent studies have shown that Vorinostat, a histone deacetylase (HDAC) inhibitor, can cause significant changes in gene expression and signaling pathways in NK cells. Since gene expression in eukaryotic cells is closely linked to the complex three-dimensional (3D) chromatin architecture, an integrative analysis of the transcriptome, histone profiling, chromatin accessibility, and 3D genome organization is needed to gain a more comprehensive understanding of how Vorinostat impacts transcription regulation of NK cells from a chromatin-based perspective. The results demonstrate that Vorinostat treatment reprograms the enhancer landscapes of the human NK-92 NK cell line while overall 3D genome organization remains largely stable. Moreover, we identified that the Vorinostat-induced RUNX3 acetylation is linked to the increased enhancer activity, leading to elevated expression of immune response-related genes via long-range enhancer-promoter chromatin interactions. In summary, these findings have important implications in the development of new therapies for cancer and immune-related diseases by shedding light on the mechanisms underlying Vorinostat's impact on transcriptional regulation in NK cells within the context of 3D enhancer network.

• Journal of Microbiology and Biotechnology
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• v.26 no.12
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• pp.2019-2029
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• 2016

Zinc finger proteins are among the most extensively applied metalloproteins in the field of biotechnology owing to their unique structural and functional aspects as transcriptional and translational regulators. The classical zinc fingers are the largest family of zinc proteins and they provide critical roles in physiological systems from prokaryotes to eukaryotes. Two cysteine and two histidine residues ($Cys_2His_2$) coordinate to the zinc ion for the structural functions to generate a ${\beta}{\beta}{\alpha}$ fold, and this secondary structure supports specific interactions with their binding partners, including DNA, RNA, lipids, proteins, and small molecules. In this account, the structural similarity and differences of well-known $Cys_2His_2$-type zinc fingers such as zinc interaction factor 268 (ZIF268), transcription factor IIIA (TFIIIA), GAGA, and Ros will be explained. These proteins perform their specific roles in species from archaea to eukaryotes and they show significant structural similarity; however, their aligned amino acids present low sequence homology. These zinc finger proteins have different numbers of domains for their structural roles to maintain biological progress through transcriptional regulations from exogenous stresses. The superimposed structures of these finger domains provide interesting details when these fingers are applied to specific gene binding and editing. The structural information in this study will aid in the selection of unique types of zinc finger applications in vivo and in vitro approaches, because biophysical backgrounds including complex structures and binding affinities aid in the protein design area.

• Molecules and Cells
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• v.45 no.7
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• pp.444-453
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• 2022

Multivalent macromolecular interactions underlie dynamic regulation of diverse biological processes in ever-changing cellular states. These interactions often involve binding of multiple proteins to a linear lattice including intrinsically disordered proteins and the chromosomal DNA with many repeating recognition motifs. Quantitative understanding of such multivalent interactions on a linear lattice is crucial for exploring their unique regulatory potentials in the cellular processes. In this review, the distinctive molecular features of the linear lattice system are first discussed with a particular focus on the overlapping nature of potential protein binding sites within a lattice. Then, we introduce two general quantitative frameworks, combinatorial and conditional probability models, dealing with the overlap problem and relating the binding parameters to the experimentally measurable properties of the linear lattice-protein interactions. To this end, we present two specific examples where the quantitative models have been applied and further extended to provide biological insights into specific cellular processes. In the first case, the conditional probability model was extended to highlight the significant impact of nonspecific binding of transcription factors to the chromosomal DNA on gene-specific transcriptional activities. The second case presents the recently developed combinatorial models to unravel the complex organization of target protein binding sites within an intrinsically disordered region (IDR) of a nucleoporin. In particular, these models have suggested a unique function of IDRs as a molecular switch coupling distinct cellular processes. The quantitative models reviewed here are envisioned to further advance for dissection and functional studies of more complex systems including phase-separated biomolecular condensates.

• Journal of Microbiology and Biotechnology
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• v.33 no.3
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• pp.319-328
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• 2023

Malassezia and Staphylococcus are the most dominant genera in human skin microbiome. To explore the inter-kingdom interactions between the two genera, we examined the transcriptional changes in Malassezia and Staphylococcus species induced upon co-culturing. RNA-seq analyses revealed that genes encoding ribosomal proteins were upregulated, while those encoding aspartyl proteases were downregulated in M. restricta after co-culturing with Staphylococcus species. We identified MRET_3770 as a major secretory aspartyl protease coding gene in M. restricta through pepstatin-A affinity chromatography followed by mass spectrometry and found that the expression of MRET_3770 was significantly repressed upon co-culturing with Staphylococcus species or by incubation in media with reduced pH. Moreover, biofilm formation by Staphylococcus aureus was inhibited in the spent medium of M. restricta, suggesting that biomolecules secreted by M. restricta such as secretory aspartyl proteases may degrade the biofilm structure. We also examined the transcriptional changes in S. aureus co-cultured with M. restricta and found co-cultured S. aureus showed increased expression of genes encoding ribosomal proteins and downregulation of those involved in riboflavin metabolism. These transcriptome data of co-cultured fungal and bacterial species demonstrate a dynamic interplay between the two co-existing genera.

• BMB Reports
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• v.43 no.2
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• pp.103-109
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• 2010

Modification of proteins by the reversible covalent addition of the small ubiquitin like modifier (SUMO) protein has important consequences affecting target protein stability, sub-cellular localization, and protein-protein interactions. SUMOylation involves a cascade of enzymatic reactions, which resembles the process of ubiquitination. In this study, we characterized the SUMOylation system from an important crop plant, rice, and show that it responds to cold, salt and ABA stress conditions on a protein level via the accumulation of SUMOylated proteins. We also characterized the transcriptional regulation of individual SUMOylation cascade components during stress and development. During stress conditions, majority of the SUMO cascade components are transcriptionally down regulated. SUMO conjugate proteins and SUMO cascade component transcripts accumulated differentially in various tissues during plant development with highest levels in reproductive tissues. Taken together, these data suggest a role for SUMOylation in rice development and stress responses.