• Molecules and Cells
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• v.44 no.5
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• pp.342-355
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• 2021

The microphthalmia-associated transcription factor family (MiT family) proteins are evolutionarily conserved transcription factors that perform many essential biological functions. In mammals, the MiT family consists of MITF (microphthalmia-associated transcription factor or melanocyte-inducing transcription factor), TFEB (transcription factor EB), TFE3 (transcription factor E3), and TFEC (transcription factor EC). These transcriptional factors belong to the basic helix-loop-helix-leucine zipper (bHLH-LZ) transcription factor family and bind the E-box DNA motifs in the promoter regions of target genes to enhance transcription. The best studied functions of MiT proteins include lysosome biogenesis and autophagy induction. In addition, they modulate cellular metabolism, mitochondria dynamics, and various stress responses. The control of nuclear localization via phosphorylation and dephosphorylation serves as the primary regulatory mechanism for MiT family proteins, and several kinases and phosphatases have been identified to directly determine the transcriptional activities of MiT proteins. In different immune cell types, each MiT family member is shown to play distinct or redundant roles and we expect that there is far more to learn about their functions and regulatory mechanisms in host defense and inflammatory responses.

• 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.5 no.4
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• pp.253-262
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• 2000

Aspergillus is considered to be an attractive host for heterologous protein production because of its safety and ability to secrete large amounts of proteins. In order to obtain high productivity, thus far promoters of amylases have been most widely used in A. oryzae. Recent progress in cloning and expression analysis, including EST sequencing, revealed that glycolytic genes represent some of those most strongly expressed in A. oryzae. Therefore, promoters of glycolytic genes could be important alternatives to promoters of amylases because lower amounts of proteases are produced in the presence of glucose. Several A. oryzae transcription factors responsible for the induction and/or maximum expression of many industrially important genes encoding amylases and proteases have been cloned and characterized. In addition to the transcriptional regulatory factors, the gene encoding the largest subunit of RNa polymerase II, constituting the basic transcription machinery, has also been cloned from A. oryzae. This recently acquired understanding of the details of transcriptional regulatory mechanisms and factors will facilitate engineering flexible controls for the expression of proteins important for the fermentation industries.

• BMB Reports
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• v.42 no.12
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• pp.823-828
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• 2009

Techniques for analyzing protein-DNA interactions on a genome-wide scale have recently established regulatory roles for distal enhancers. However, the large sizes of higher eukaryotic genomes have made identification of these elements difficult. Information regarding sequence conservation, exon annotation and repetitive regions can be used to reduce the size of the search region. However, previously developed resources are inadequate for consolidating such information. CONVIRT is a web resource for the identification of transcription factor binding sites and also features comparative genomics. Genomic information on ortholog-independent conserved regions, exons, repeats and sequences is integrated into the virtual chromosome, and statistically over-represented single or combinations of transcription factor binding sites are sought. CONVIRT provides regulatory network analysis for several organisms with long promoter regions and permits inter-species genome alignments. CONVIRT is freely available at http://biosoft.kaist.ac.kr/convirt.

• Journal of Periodontal and Implant Science
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• v.40 no.1
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• pp.39-44
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• 2010

Purpose: Bone tissues for clinical application can be improved by studies on osteoblast differentiation. Runx2 is known to be an important transcription factor for osteoblast differentiation. However, bone morphogenetic protein (BMP)-2 treatment to stimulate Runx2 is not sufficient to acquire enough bone formation in osteoblasts. Therefore, it is necessary to find other regulatory factors which can improve the transcriptional activity of Runx2. The erythroblast transformation-specific (ETS) transcription factor family is reported to be involved in various aspects of cellular proliferation and differentiation. Methods: We have noticed that the promoters of osteoblast differentiation markers such as alkaline phosphatase (Alp), osteopontin (Opn), and osteocalcin (Oc) contain Ets binding sequences which are also close to Runx2 binding elements. Luciferase assays were performed to measure the promoter activities of these osteoblast differentiation markers after the transfection of Runx2, myeloid Elf-1-like factor (MEF), and Runxs+MEF. Reverse-transcription polymerase chain reaction was also done to check the mRNA levels of Opn after Runx2 and MEF transfection into rat osteoblast (ROS) cells. Results: We have found that MEF, an Ets transcription factor, increased the transcriptional activities of Alp, Opn, and Oc. The addition of Runx2 resulted in the 2- to 6-fold increase of the activities. This means that these two transcription factors have a synergistic effect on the osteoblast differentiation markers. Furthermore, early introduction of these two Runx2 and MEF factors significantly elevated the expression of the Opn mRNA levels in ROS cells. We also showed that Runx2 and MEF proteins physically interact with each other. Conclusions: Runx2 interacts with MEF proteins and binds to the promoters of the osteoblast markers such as Opn nearby MEF to increase its transcriptional activity. Our results also imply that osteoblast differentiation and bone formation can be increased by activating MEF to elicit the synergistic effect of Runx2 and MEF.

• Genomics & Informatics
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• v.5 no.4
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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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• v.48 no.11
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• pp.599-608
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• 2015

Regeneration, a process of reconstitution of the entire tissue, occurs throughout life in the olfactory epithelium (OE). Regeneration of OE consists of several stages: proliferation of progenitors, cell fate determination between neuronal and non-neuronal lineages, their differentiation and maturation. How the differentiated cell types that comprise the OE are regenerated, is one of the central questions in olfactory developmental neurobiology. The past decade has witnessed considerable progress regarding the regulation of transcription factors (TFs) involved in the remarkable regenerative potential of OE. Here, we review current state of knowledge of the transcriptional regulatory networks that are powerful modulators of the acquisition and maintenance of developmental stages during regeneration in the OE. Advance in our understanding of regeneration will not only shed light on the basic principles of adult plasticity of cell identity, but may also lead to new approaches for using stem cells and reprogramming after injury or degenerative neurological diseases.

• Journal of Microbiology and Biotechnology
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• v.9 no.4
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• pp.488-497
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• 1999

Probing Streptomyces albus ATCC 21838 chromosomal DNA with a proline tRNA sequence resulted in an isolation of a putative integrating element in the 6.4-kb EcoRI fragment. It was found that Streptomyces lividans TK-24 transformed with a cloned DNA fragment on a multicopy plasmid, produced a higher level of spore pigment and mycelial red pigment on a regeneration agar. Furthermore, the transformant S. lividans TK-24 produced a markedly increased level of undecylprodigiosin in a broth culture. A nucleotide sequence analysis of the cloned region revealed several open reading frames homologous to the integrases of integrating plasmids or temperate bacteriophages, signal-transducing regulatory proteins with a conserved ATP-binding domain, oxidoreductases ($\beta$-ketoacyl reductase), and an AraC-like transcriptional regulator. To examine the effect on antibiotic production, each coding region was overexpressed separately from the other genes in the region in S. lividans TK-24 with; pJHS3044 for the expression of the signal-transducing regulatory protein homologue, pJHS3045 for the homologue of oxidoreductase, and pJHS3051 for the homologue of the AraC-like transcriptional regulator. Phenotypic studies of S. lividans TK-24 strains harboring plasmids for the overexpression of individual genes suggested the following effects of the genes on antibiotic production: The oxidoreductase homologue stimulated the production of actinorhodin and undecylprodigiosin, which was influenced by the culture conditions; the homologue of the AraC-like transcriptional regulator was the most effective factor in antibiotic production within all the culture conditions tested; the signal-transducing regulatory protein homologue repressed the effect due to the homologue of the AraC-like transcriptional regulator, however, the antibiotic production was derepressed upon entering the stationary phase.

• Molecules and Cells
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• v.45 no.4
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• pp.243-256
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• 2022

Transcriptional regulation, a core component of gene regulatory networks, plays a key role in controlling individual organism's growth and development. To understand how plants modulate cellular processes for growth and development, the identification and characterization of gene regulatory networks are of importance. The SHORT-ROOT (SHR) transcription factor is known for its role in cell divisions in Arabidopsis (Arabidopsis thaliana). However, whether SHR is involved in hypocotyl cell elongation remains unknown. Here, we reveal that SHR controls hypocotyl cell elongation via the transcriptional regulation of XTH18, XTH22, and XTH24, which encode cell wall remodeling enzymes called xyloglucan endotransglucosylase/hydrolases (XTHs). Interestingly, SHR activates transcription of the XTH genes, independently of its partner SCARECROW (SCR), which is different from the known mode of action. In addition, overexpression of the XTH genes can promote cell elongation in the etiolated hypocotyl. Moreover, confinement of SHR protein in the stele still induces cell elongation, despite the aberrant organization in the hypocotyl ground tissue. Therefore, it is likely that SHR-mediated growth is uncoupled from SHR-mediated radial patterning in the etiolated hypocotyl. Our findings also suggest that intertissue communication between stele and endodermis plays a role in coordinating hypocotyl cell elongation of the Arabidopsis seedling. Taken together, our study identifies SHR as a new crucial regulator that is necessary for cell elongation in the etiolated hypocotyl.

• Archives of Pharmacal Research
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• v.25 no.2
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• pp.208-213
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• 2002

The human polyomavirus JC virus is the etiologic agent of progressive multifocal leukoencephalopathy (PML). As the JC virus early promoter directs cell-specific expression of the viral replication factor large T antigen, transcriptional regulation constitutes a major mechanism of glial tropism in PML. It has been demonstrated that SV4O or JC virus large T antigen interacts with p53 protein and regulates many viral and cellular genes. In this study we founts that p53 represses the JC virus early promoter in both glial and nonglial cells To identify the cis-regulatory elements responsible for p53-mediated repression, deletional and site-directed mutational analyses were performed . Deletion of the enhancer region diminished p53-mediated transcriptional repression. However, point mutations of several transcription factor binding sites in the basal promoter region did not produce any significant changes. In support of this observation, when the enhancer was fused to a heterologous promoter, p53 red reduced the promoter activity about three fold. These results indicate that the enhancer region is important for tole repression of JC virus transcription by p53. Furthermore, coexpression of JC virus T antigen with a p53 protein abolished p53-mediated repression of the JC virus early promoter in non-glial cells, but not in glial cells. This finding suggests that T antigen interacts with p53 and regulates JC virus transcription in a cell-specific manner.