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

• Genomics & Informatics
• /
• 제10권3호
• /
• pp.145-152
• /
• 2012

Chromatin structure and dynamics that are influenced by epigenetic marks, such as histone modification and DNA methylation, play a crucial role in modulating gene transcription. To understand the relationship between histone modifications and regulatory elements in breast cancer cells, we compared our chromatin immunoprecipitation sequencing (ChIP-Seq) histone modification patterns for histone H3K4me1, H3K4me3, H3K9/16ac, and H3K27me3 in MCF-7 cells with publicly available formaldehyde-assisted isolation of regulatory elements (FAIRE)-chip signals in human chromosomes 8, 11, and 12, identified by a method called FAIRE. Active regulatory elements defined by FAIRE were highly associated with active histone modifications, like H3K4me3 and H3K9/16ac, especially near transcription start sites. The H3K9/16ac-enriched genes that overlapped with FAIRE signals (FAIRE-H3K9/14ac) were moderately correlated with gene expression levels. We also identified functional sequence motifs at H3K4me1-enriched FAIRE sites upstream of putative promoters, suggesting that regulatory elements could be associated with H3K4me1 to be regarded as distal regulatory elements. Our results might provide an insight into epigenetic regulatory mechanisms explaining the association of histone modifications with open chromatin structure in breast cancer cells.

• Molecules and Cells
• /
• 제45권8호
• /
• pp.522-530
• /
• 2022

Transposable elements (TEs) account for approximately 45% of the human genome. TEs have proliferated randomly and integrated into functional genes during hominoid radiation. They appear as right-handed B-DNA double helices and slightly elongated left-handed Z-DNAs. Human endogenous retrovirus (HERV) families are widely distributed in human chromosomes at a ratio of 8%. They contain a 5'-long terminal repeat (LTR)-gag-pol-env-3'-LTR structure. LTRs contain the U3 enhancer and promoter region, transcribed R region, and U5 region. LTRs can influence host gene expression by acting as regulatory elements. In this review, we describe the alternative promoters derived from LTR elements that overlap Z-DNA by comparing Z-hunt and DeepZ data for human functional genes. We also present evidence showing the regulatory activity of LTR elements containing Z-DNA in GSDML. Taken together, the regulatory activity of LTR elements with Z-DNA allows us to understand gene function in relation to various human diseases.

• Asian-Australasian Journal of Animal Sciences
• /
• 제14권11호
• /
• pp.1628-1633
• /
• 2001

A goat ${\beta}$-casein gene was cloned and sequenced. Our previous study had determined the nucleotide sequences of the 5' flanking region and the structural gene including all 9 exons. In the present study, investigations were done on the regulatory sequences in the 5' flanking region of the goat ${\beta}$-casein gene by aligning and comparing it with the same gene from other mammals. The results showed that -200/-1 bp of the 5' flanking sequences contained six conserved clusters, in which the sites of gene expression regulated by the transcription factor and hormone might exist. It showed that fourteen glucocorticoid receptor elements, two cAMP responsive elements, two SV40 virus enhancer core sequences, two OCT-1 binding elements and one CTF/NF-1 binding element were dispersed in the 5' flanking region of goat ${\beta}$-casein gene. Our findings are perhaps valuable for the elucidation of the molecular mechanisms that control the expression of the goat ${\beta}$-casein gene.

• 한국식물학회:학술대회논문집
• /
• 한국식물학회 1987년도 식물생명공학 심포지움 논문집 Proceedings of Symposia on Plant Biotechnology
• /
• pp.241-260
• /
• 1987

The regulatory mechanisms of gene expression in higher plant were not ascertained in detail because the genome size is very large and complex. However, the above-mentioned study is remarkably progressed in parallel with development of DNA recombinant technology and plant vector system. Some research results connected with the mechanisms could be summarized as follows. 1. Many plant genes including chloroplast genes are cloned. 2. The structures of some regulatory regions of gene expression are determined, and it is confirmed that new regulatory units are made by transposable elements. 3. Plant gene expression is regulated not only at transcriptional level but also at translational level. 4. The factors that regulate plant gene expression could be divided as two categorys. One is endogenous elements including the structural change of chromatin during development stage and tissue differentiation. The other is environmental stimulations such as air, water, heat, salts and light. However, some sufficient research-aid fund is essential in order to study the regulatory mechanisms of gene expression more systematically.

• Journal of Microbiology and Biotechnology
• /
• 제15권3호
• /
• pp.551-559
• /
• 2005

The recent rapid increase in genomic data related to many microorganisms and the development of computational tools to accurately analyze large amounts of data have enabled us to design several kinds of simulation approaches for the complex behaviors of cells. Among these approaches, dFBA (dynamic flux balance analysis), which utilizes FBA, differential equations, and regulatory events, has correctly predicted cellular behaviors under given environmental conditions. However, until now, dFBA has centered on substrate concentration, cell growth, and gene on/off, but a detailed hierarchical structure of a regulatory network has not been taken into account. The use of Boolean rules for regulatory events in dFBA has limited the representation of interactions between specific regulatory proteins and genes and the whole transcriptional regulation mechanism with environmental change. In this paper, we adopted the operon as the basic structure, constructed a hierarchical structure for a regulatory network with defined fundamental symbols, and introduced a weight between symbols in order to solve the above problems. Finally, the total control mechanism of regulatory elements (operons, genes, effectors, etc.) with time was simulated through the linkage of dFBA with regulatory network modeling. The lac operon, trp operon, and tna operon in the central metabolic network of E. coli were chosen as the basic models for control patterns. The suggested modeling method in this study can be adopted as a basic framework to describe other transcriptional regulations, and provide biologists and engineers with useful information on transcriptional regulation mechanisms under extracellular environmental change.

• Genomics & Informatics
• /
• 제11권1호
• /
• pp.2-6
• /
• 2013

Until recently, since the Human Genome Project, the general view has been that the majority of the human genome is composed of junk DNA and has little or no selective advantage to the organism. Now we know that this conclusion is an oversimplification. In April 2003, the National Human Genome Research Institute (NHGRI) launched an international research consortium called Encyclopedia of DNA Elements (ENCODE) to uncover non-coding functional elements in the human genome. The result of this project has identified a set of new DNA regulatory elements, based on novel relationships among chromatin accessibility, histone modifications, nucleosome positioning, DNA methylation, transcription, and the occupancy of sequence-specific factors. The project gives us new insights into the organization and regulation of the human genome and epigenome. Here, we sought to summarize particular aspects of the ENCODE project and highlight the features and data that have recently been released. At the end of this review, we have summarized a case study we conducted using the ENCODE epigenome data.

• 법제연구
• /
• 제41호
• /
• pp.401-434
• /
• 2011

급격한 방송통신 융합 현상의 진전으로 인해 기존 수직적 규제체계의 한계를 극복하기 위해 수평적 규제체계 도입이 논의되고 있다. 하지만 수평적 규제체계도 생태계 산업구조의 등장으로 인해 한계를 노출하고 있다. 방송통신 생태계가 구축된 경우의 경쟁상황은 개별 사업자간 경쟁을 전제한 경쟁상황과는 다른 모습으로 나타난다. 중추적 사업자의 사업전략에 따라 다양한 구조의 생태계가 존재하게 되고, 이러한 중추적 사업자의 역량이 생태계 간 경쟁의 핵심이 된다. 그런데, 중추적 사업자의 특성이나 사업 전략에 따라 그가 존재하는 계층 영역이 달라질 수 있으므로, 생태계 간 경쟁 환경에 수평적 규제체계를 그대로 적용할 경우 일반적으로 경제적 규제의 강도가 약한 콘텐츠 계층에 중추적 사업자가 존재하는 생태계는 전송 계층에 중추적 사업자가 위치하는 생태계에 비해 상대적으로 약한 규제를 받게 되어 생태계에 따라 규제 차등화가 발생하게 되고 이는 생태계간 경쟁왜곡 현상을 초래하는 제도적 원인이 될 수 있다. 이러한 경쟁왜곡 현상을 완화하기 위한 방안으로서 생태계 요소를 반영한 방송통신 규제체계로는 전혀 새로운 규제체계를 정립하는 방안과 기존 제도를 활용하는 두 가지 방안을 상정할 수 있다. 그러나 방송통신 생태계가 너무 복잡하여 다양한 시장변화 동인 모두를 적절하게 포괄하는 유효경쟁에 관한 단일한 기준을 도출하기 어려운 현 상황에서 전혀 새로운 규제체계를 마련하는 것은 비현실적이다. 따라서 이 글에서는 수평적 규제체계를 전제로 하면서도 생태계 요소를 반영하는 규제체계를 정립하는 방안으로 경쟁상황평가제도에 생태계 요소를 반영하고 경쟁상황평가제도와 구체적인 규제수단 마련의 연계성을 강화하는 방안을 제안하였다. 이러한 방안은 수평적 규제체계를 집행하기 위한 사업자분류체계로서 논의되는 2단계 분류체계나 3단계 분류체계 어느 것과도 결합될 수 있다. 그러나 기존의 분류체계에 의하더라도 전송 기능을 담당하고 있지는 않지만 최근 디지털 콘텐츠 유통에서 중요한 역할을 담당하고 있는 앱스토어 등은 규제 영역 밖에 놓이게 될 수 있다. 따라서 이를 플랫폼으로 파악해 규제할 수 있도록 플랫폼 개념을 확대하고 이러한 플랫폼을 제공하는 사업자를 2단계 분류체계 또는 3단계 분류체계 내로 위치지우는 방식으로주제어:수평적 규제체계, 생태계, 전송단계, 콘텐츠 단계, 중추적 사업자, 상당한 지배력을 가진 사업자(SMP), 방송법, 통신법 사업자 분류체계를 구성하는 것이 타당하다고 생각한다.

• Molecules and Cells
• /
• 제41권4호
• /
• pp.342-350
• /
• 2018

Flowering time is determined by florigens. These genes include, Heading date 3a (Hd3a) and Rice FT 1 (RFT1) in rice, which are specifically expressed in the vascular tissues of leaves at the floral transition stage. To study the cis-regulatory elements present in the promoter region of Hd3a, we generated transgenic plants carrying the 1.75-kb promoter fragment of Hd3a that was fused to the ${\beta}$-glucuronidase (GUS) reporter gene. Plants expressing this construct conferred a vascular cell-specific expression pattern for the reporter gene. However, GUS was expressed in leaves at all developmental stages, including the early seedling stage when Hd3a was not detected. Furthermore, the reporter was expressed in roots at all stages. This suggests that the 1.75-kb region lackings cis-elements that regulate leaf-specific expression at the appropriate developmental stages. Deletion analyses of the promoter region indicated that regulatory elements determining vascular cell-specific expression are present in the 200-bp region between -245 bp and -45 bp from the transcription initiation site. By transforming the Hd3a-GUS construct to rice cultivar 'Taichung 65' which is defective in Ehd1, we observed that Ehd1 is the major regulatory element that controls Hd3a promoter activity.

• Journal of Applied Biological Chemistry
• /
• 제42권2호
• /
• pp.62-65
• /
• 1999

Iron regulatory proteins (IRPs) 1 and 2 bind with equally high affinity to specific RNA stem-loop sequences known as iron-responsive elements (IRE) which mediate the post-transcriptional regulation of many genes of iron metabolism. To study putative IRE-like sequences in RNA transcripts using the IRP-IRE interaction, Eight known genes from database were selected and the RNA binding activity of IRE-like sequences were compared to IRP-2. Among them, the IRE-like sequence in 3'-untranslational region (UTR) of divalent ration transporter-1 (DCT-1) shows a significant RNA binding affinity. This finding predicts that IRE consensus sequence present within 3'-UTR of DCT-1 might confer the regulation by IRP-2.