• 한국생물물리학회:학술대회논문집
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• 한국생물물리학회 2003년도 정기총회 및 학술발표회
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• pp.49-49
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• 2003

BldD is one of a set of morphological differentiation regulators in Streptomyces coelicolor. The bldD coding region was cloned and heterologously expressed in Escherichia coli. Previous analysis showed the splitting appearance of purified BldD.

• Clinical and Experimental Reproductive Medicine
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• 제38권2호
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• pp.61-67
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• 2011

Recently, a significant understanding of the molecular mechanisms regulating spermatogenesis has been achieved utilizing small RNA molecules (small RNAs), including small interfering RNAs (siRNAs), microRNAs (miRNAs), and Piwi-interacting RNAs (piRNAs) which emerged as important regulators of gene expression at the post-transcriptional or translation level. piRNAs are only present in pachytene spermatocytes and round spermatids, whereas miRNAs are expressed abundantly in male germ cells throughout spermatogenesis. This review is aimed at providing a glimpse of piRNAs and their interacting family proteins such as PIWIL1, PIWIL2, and PIWIL4 in spermatogenesis.

• Molecules and Cells
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• 제40권1호
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• pp.10-16
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• 2017

When peripheral axons are damaged, neuronal injury signaling pathways induce transcriptional changes that support axon regeneration and consequent functional recovery. The recent development of bioinformatics techniques has allowed for the identification of many of the regeneration-associated genes that are regulated by neural injury, yet it remains unclear how global changes in transcriptome are coordinated. In this article, we review recent studies on the epigenetic mechanisms orchestrating changes in gene expression in response to nerve injury. We highlight the importance of epigenetic mechanisms in discriminating efficient axon regeneration in the peripheral nervous system and very limited axon regrowth in the central nervous system and discuss the therapeutic potential of targeting epigenetic regulators to improve neural recovery.

• Journal of Cancer Prevention
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• 제23권4호
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• pp.162-169
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• 2018

$TGF-{\beta}$ signaling plays a tumor suppressive role in normal and premalignant cells but promotes tumor progression during the late stages of tumor development. The $TGF-{\beta}$ signaling pathway is tightly regulated at various levels, including transcriptional and post-translational mechanisms. Ubiquitination of signaling components, such as receptors and Smad proteins is one of the key regulatory mechanisms of $TGF-{\beta}$ signaling. Tripartite motif (TRIM) family of proteins is a highly conserved group of E3 ubiquitin ligase proteins that have been implicated in a variety of cellular functions, including cell growth, differentiation, immune response, and carcinogenesis. Recent emerging studies have shown that some TRIM family proteins function as important regulators in tumor initiation and progression. This review summarizes current knowledge of TRIM family proteins regulating the $TGF-{\beta}$ signaling pathway with relevance to cancer.

• 한국동물학회:학술대회논문집
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• 한국동물학회 1998년도 한국생물과학협회 학술발표대회
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• pp.113-113
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• 1998

In Saccharomyces cerevisiae UV irradiation and a variety of chemical DNA -damaging agents induce the transcription of specific genes, including several involved in DNA repair. One of the best characterized of DNA -damage inducible genes is PHRI, which encodes the apoenzyme for DNA photolyase. Basal-level and damage-induced expression of PHRI require an upstream activation sequence, UASPHRI. Here we report the identification of the UlvIE6 gene of S. cerevisiae as a regulator of UASPHRl activity. Surprisingly, the effect of deletion of UME6 is growth phase dependent. In wild-type cells PHRI is induced in late exponential phase, concomitant with the initiation of glycogen accumulation that precedes the diauxic shift. Deletion of UNIE6 abolishes this induction, decreases the steady-state concentration of photolyase molecules and PHRI mRNA, and increases the UV sensitivity of a rad2 mutant. The results suggest that UM E6 contributes to the regulated expression of a subset of damage-responsive genes in yeast. Furthermore, the upstream repression sequence, URSPHRI, is required for repression and damage-induced expression of PHRl. Here we show identification of YER169W and YDR096W as putative regulators acting through $URS_{PHRI}$. These open reading frames were designated as RPHI (YERl69W) and RPH2 (YDR096W) indicating regulator of PHRI. Simultaneous disruption of both genes showed a synergistic effect, producing a four-fold increase in basal level expression and a similar decrease m the induction ratio following treatment of methyl methanesulfonate(MMS). Mutation of the sequence ($AG_4$) bound by Rphlp rendered the promoter of PHRI insensitive to changes in RPHI or RPH2 status. The data suggest that RPHI and RPH2 act as damage-responsive negative regulators of PHRI. Surprisingly, the sequence bound by Rphlp in vitro is found to be $AG_4$ which is identical to the consensus binding site for the regulators Msn2p and Msn4p involved in stress-induced expression. Deletion of MSN2 and MSN4 has little effect on the induction$.$ ratio following DNA damage. However, all deletions led to a significant decrease in basal-level and induced expression of PHRI. These results imply that MSN2 and MSN4 are positive regulators of P HRI but are not required for DNA damage repression. [Supported by grant from NIH]om NIH]

• Asian-Australasian Journal of Animal Sciences
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• 제32권5호
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• pp.614-628
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• 2019

Objective: The inhibitory leukocyte immunoglobulin-like receptors (LILRBs) play an important role in innate immunity. The present study represents the first description of the cloning and structural and functional analysis of LILRB1 and LILRB3 isolated from two genetically disparate chicken lines. Methods: Chicken LILRB1-3 genes were identified by bioinformatics approach. Expression studies were performed by transfection, quantitative polymerase chain reaction. Signal transduction was analyzed by western blots, immunoprecipitation and flow cytometric. Cytokine levels were determined by enzyme-linked immunosorbent assay. Results: Amino acid homology and phylogenetic analyses showed that the homologies of LILRB1 and LILRB3 in the chicken line 6.3 to those proteins in the chicken line 7.2 ranged between 97%-99%, while homologies between chicken and mammal proteins ranged between 13%-19%, and 13%-69%, respectively. Our findings indicate that LILRB1 and LILRB3 subdivided into two groups based on the immunoreceptor tyrosine-based inhibitory motifs (ITIM) present in the transmembrane domain. Chicken line 6.3 has two ITIM motifs of the sequence LxYxxL and SxYxxV while line 7.2 has two ITIM motifs of the sequences LxYxxL and LxYxxV. These motifs bind to SHP-2 (protein tyrosine phosphatase, non-receptor type 11) that plays a regulatory role in immune functions. Moreover, our data indicate that LILRB1 and LILRB3 associated with and activated major histocompatibility complex (MHC) class I and ${\beta}2-microglobulin$ and induced the expression of transporters associated with antigen processing, which are essential for MHC class I antigen presentation. This suggests that LILRB1 and LILRB3 are transcriptional regulators, modulating the expression of components in the MHC class I pathway and thereby regulating immune responses. Furthermore, LILRB1 and LILRB3 activated Janus kinase2/tyrosine kinase 2 (JAK2/TYK2); signal transducer and activator of transcription1/3 (STAT1/3), and suppressor of cytokine signaling 1 genes expressed in Macrophage (HD11) cells, which induced Th1, Th2, and Th17 cytokines. Conclusion: These data indicate that LILRB1 and LILRB3 are innate immune receptors associated with SHP-2, MHC class I, ${\beta}2-microglobulin$, and they activate the Janus kinase/signal transducer and activator of transcription signaling pathway. Thus, our study provides novel insights into the regulation of immunity and immunopathology.

• Genomics & Informatics
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• 제5권4호
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• pp.143-151
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• 2007

To understand the mechanism of transcriptional regulation, it is essential to detect promoters and regulatory elements. Various kinds of methods have been introduced to improve the prediction accuracy of regulatory elements. Since there are few experimentally validated regulatory elements, previous studies have used criteria based solely on the level of scores over background sequences. However, selecting the detection criteria for different prediction methods is not feasible. Here, we studied the calibration of thresholds to improve regulatory element prediction. We predicted a regulatory element using MATCH, which is a powerful tool for transcription factor binding site (TFBS) detection. To increase the prediction accuracy, we used a regulatory potential (RP) score measuring the similarity of patterns in alignments to those in known regulatory regions. Next, we calibrated the thresholds to find relevant scores, increasing the true positives while decreasing possible false positives. By applying various thresholds, we compared predicted regulatory elements with validated regulatory elements from the Open Regulatory Annotation (ORegAnno) database. The predicted regulators by the selected threshold were validated through enrichment analysis of muscle-specific gene sets from the Tissue-Specific Transcripts and Genes (T-STAG) database. We found 14 known muscle-specific regulators with a less than a 5% false discovery rate (FDR) in a single TFBS analysis, as well as known transcription factor combinations in our combinatorial TFBS analysis.

• BMB Reports
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• 제42권9호
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• pp.593-598
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• 2009

Cell cycle progression is regulated by both transcriptional and post-transcriptional mechanisms. MicroRNAs (miRNAs) emerge as a new class of small non-coding RNA regulators of cell cycle as recent evidence suggests. It is hypothesized that expression of specific miRNAs oscillates orderly along with cell cycle progression. However, the oscillated expression patterns of many candidate miRNAs have yet to be determined. Here, we describe miRNA expression profiling in double-thymidine synchronized HeLa cells as cell cycle progresses. Twenty-five differentially expressed miRNAs were classified into five groups based on their cell cycle-dependent expression patterns. The cyclic expression of six miRNAs (miR-221, let-7a, miR-21, miR-34a, miR-24, miR-376b) was validated by real-time quantitative RT-PCR (qRT-PCR). These results suggest that specific miRNAs, along with other key factors are required for maintaining and regulating proper cell cycle progression. The study deepens our understanding on cell cycle regulation.

• Journal of Microbiology
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• 제40권4호
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• pp.305-312
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• 2002

The effects of two natural polyamines (putrescine and spermidine) on the synthesis of ArcA, a response regulator of the Arc two-component signal transduction system, were studied using an E. coli mutant deficient in polyamine biosynthesis. Endogenous polyamine deficiency of the mutant resulted in marked reduction in the ArcA level determined by Western blot analysis. Putrescine supplement to the growth medium effectively increased the ArcA level of the mutant in a concentration-dependent manner. Spermidine also stimulated the ArcA level in the mutant to a greater degree than putrescine. Expression of arcA'::lacZ operon fusion in the mutant was stimulated 6-fold and 10-fold by putrescine and spermidine at a 1mM concentration, respectively, indicating that the stimulatory effect of the polyamines on ArcA synthesis is due to transcriptional induction, and that spermidine is a more potent arcA inducer than putrescine. The polyamine-dependent arcA'::lacZ induction was growth-phase-dependent and independent of either arcA or fnr which are two regulators involved in anaerobic stimulation of the Arch level. These results suggested that putrescine and spermidine polyamines may be potential intracellular signal molecules in the control of arcA expression, and thereby may play an important role in cellular metabolism.

• Molecules and Cells
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• 제43권6호
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• pp.517-529
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• 2020

Carboxyl-terminal binding proteins (CtBPs) are transcription regulators that control gene expression in multiple cellular processes. Our recent findings indicated that overexpression of CtBP2 caused the repression of multiple bone development and differentiation genes, resulting in atrophic nonunion. Therefore, disrupting the CtBP2-associated transcriptional complex with small molecules may be an effective strategy to prevent nonunion. In the present study, we developed an in vitro screening system in yeast cells to identify small molecules capable of disrupting the CtBP2-p300 interaction. Herein, we focus our studies on revealing the in vitro and in vivo effects of a small molecule NSM00158, which showed the strongest inhibition of the CtBP2-p300 interaction in vitro. Our results indicated that NSM00158 could specifically disrupt CtBP2 function and cause the disassociation of the CtBP2-p300-Runx2 complex. The impairment of this complex led to failed binding of Runx2 to its downstream targets, causing their upregulation. Using a mouse fracture model, we evaluated the in vivo effect of NSM00158 on preventing nonunion. Consistent with the in vitro results, the NSM00158 treatment resulted in the upregulation of Runx2 downstream targets. Importantly, we found that the administration of NSM00158 could prevent the occurrence of nonunion. Our results suggest that NSM00158 represents a new potential compound to prevent the occurrence of nonunion by disrupting CtBP2 function and impairing the assembly of the CtBP2-p300-Runx2 transcriptional complex.