• Title/Summary/Keyword: Transcriptome profile

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Vorinostat-induced acetylation of RUNX3 reshapes transcriptional profile through long-range enhancer-promoter interactions in natural killer cells

  • Eun-Chong Lee;Kyungwoo Kim;Woong-Jae Jung;Hyoung-Pyo Kim
    • 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.

Transcriptomic analysis of 'Campbell Early' and 'Muscat Bailey A' grapevine shoots exposed to freezing cold stress (영하의 저온에 노출된 'Campbell Early'와 'Muscat Bailey A' 포도나무 신초의 전사체 비교)

  • Kim, Seon Ae;Yun, Hae Keun
    • Journal of Plant Biotechnology
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    • v.43 no.2
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    • pp.204-212
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    • 2016
  • To understand the responses of grapevines in response to cold stress causing the limited growth and development, differentially expressed genes (DEGs) were screened through transcriptome analysis of shoots from 2 grapevine cultivars ('Campbell Early' and 'Muscat Baily A') kept at -$2^{\circ}C$ for 4 days. In gene ontology analysis of DEGs from 'Campbell Early', there were 17,424 clones related with biological process, 28,954 with cellular component, and 6,972 with molecular function genes in response to freezing temperature. The major induced genes included dehydrin xero 1, K-box region and MADS-box transcription factor family protein, and MYB domain protein 36, and inhibited genes included light-harvesting chlorophyll B-binding protein 3, FASCICLIN-like arabinoogalactan 9, and pectin methylesterase 61 in 'Campbell Early' grapevines. In gene ontology analysis of DEGs from 'Muscat Baily A', there were 1,157 clones related with biological process, 1,350 with cellular component, and 431 with molecular function gene. The major induced genes of 'Muscat Baily A' included NB-ARC domain-containing disease resistance protein, fatty acid hydrozylase superfamily, and isopentenyltransferase 3, and inhibited genes included binding, IAP-like protein 1, and pentatricopeptide repeat superfamily protein. All major DEGs were shown to be expressed differentially by freezing temperature in real time-PCR analysis. Protein domain analysis using InterPro Scan revealed that ubiquitin-protein ligase was redundant in both tested grapevines. Transcriptome profile of shoots exposed to cold can provide new insights into the molecular basis of tolerance to low-temperature in grapevines, and can be used as resources for development new grapevines tolerant to coldness.

Anti-proliferative Properties of p-Coumaric Acid in SNU-16 Gastric Cancer Cells (SNU-16 위암 세포주에서 p-coumaric acid의 세포성장 억제 효과)

  • Jang, Mi Gyeong;Ko, Hee Chul;Kim, Se-Jae
    • Journal of Life Science
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    • v.29 no.7
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    • pp.809-816
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    • 2019
  • The ubiquitous plant metabolite p-coumaric acid (p-CA) has antioxidant and anti-inflammatory properties, but its anti-cancer activity has not been established in gastric cancer cell lines. In this study, we investigated the effects of p-CA on the proliferation and transcriptome profile of SNU16 gastric cancer cells. Treatment with p-CA induced apoptosis of the SNU-16 cells by regulating the expression of pro-apoptotic and anti-apoptotic proteins, such as Bcl-2, poly (ADP-ribose) polymerase (PARP), Bax, procaspase-3, and cleaved-caspase-3. The genes differentially expressed in response to p-CA treatment of the SNU-16 cells were identified by RNA sequencing analysis. Genes regulated by p-CA were involved mainly in the inflammatory response, apoptotic processes, cell cycle, and immune response. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated that the phosphatidylinositol-3-kinase-Akt and cancer signaling pathways were altered by p-CA. Protein-protein interaction (PPI) network analysis also revealed that p-CA treatment was correlated with differential expression of genes associated with the inflammatory response and cancer. Collectively, these results suggest that p-CA has potential utility in gastric cancer prevention.

Expression profile of defense-related genes in response to gamma radiation stress (방사선 스트레스 반응 방어 유전자의 탐색 및 발현 분석)

  • Park, Nuri;Ha, Hye-Jeong;Subburaj, Saminathan;Choi, Seo-Hee;Jeon, Yongsam;Jin, Yong-Tae;Tu, Luhua;Kumari, Shipra;Lee, Geung-Joo
    • Journal of Plant Biotechnology
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    • v.43 no.3
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    • pp.359-366
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    • 2016
  • Tradescantia is a perennial plant in the family of Commelinaceae. It is known to be sensitive to radiation. In this study, Tradescantia BNL 4430 was irradiated with gamma radiation at doses of 50 to 1,000 mGy in a phytotron equipped with a $^{60}Co$ radiation source at Korea Atomic Energy Research Institute, Korea. At 13 days after irradiation, we extracted RNA from irradiated floral tissues for RNA-seq. Transcriptome assembly produced a total of 77, 326 unique transcripts. In plantlets exposed to 50, 250, 500, and 1000 mGy, the numbers of up-regulated genes with more than 2-fold of expression compared that in the control were 116, 222, 246, and 308, respectively. Most of the up-regulated genes induced by 50 mGy were heat shock proteins (HSPs) such as HSP 70, indicating that protein misfolding, aggregation, and translocation might have occurred during radiation stress. Similarly, highly up-regulated transcripts of the IQ-domain 6 were induced by 250 mGy, KAR-UP oxidoreductase 1 was induced by 500 mGy, and zinc transporter 1 precursor was induced by 1000 mGy. Reverse transcriptase (RT) PCR and quantitative real time PCR (qRT-PCR) further validated the increased mRNA expression levels of selected genes, consistent with DEG analysis results. However, 2.3 to 97- fold higher expression activities were induced by different doses of radiation based on qRT-PCR results. Results on the transcriptome of Tradescantia in response to radiation might provide unique identifiers to develop in situ monitoring kit for measuring radiation exposure around radiation facilities.

Annotation and Expression Profile Analysis of cDNAs from the Antarctic Diatom Chaetoceros neogracile

  • Jung, Gyeong-Seo;Lee, Choul-Gyun;Kang, Sung-Ho;Jin, Eon-Seon
    • Journal of Microbiology and Biotechnology
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    • v.17 no.8
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    • pp.1330-1337
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    • 2007
  • To better understand the gene expression of the cold-adapted polar diatom, we conducted a survey of the Chaetoceros neogracile transcriptome by cDNA sequencing and expression of interested cDNAs from the Antarctic diatom. A non-normalized cDNA library was constructed from the C. neogracile, and a total of 2,500 cDNAs were sequenced to generate 1,881 high-quality expressed sequence tags (ESTs) (accession numbers EL620615-EL622495). Based on their clustering, we identified 154 unique clusters comprising 342 ESTs. The remaining 1,540 ESTs did not cluster. The number of unique genes identified in the data set is thus estimated to be 1,694. Taking advantage of various tools and databases, putative functions were assigned to 939 (55.4%) of these genes. Of the remaining 540 (31.9%) unknown sequences, 215 (12.7%) appeared to be C. neogracile-specific since they lacked any significant sequence similarity to any sequence available in the public databases. C. neogracile consisted of a relatively high percentage of genes involved in metabolism, genetic information processing, cellular processes, defense or stress resistance, photosynthesis, structure, and signal transduction. From the ESTs, the expression of these putative C. neogracile genes was investigated: fucoxanthin chlorophyll (chl) a,c-binding protein (FCP), ascorbate peroxidase (ASP), and heat-shock protein 90 (HSP90). The abundance of ASP and HSP90 changed substantially in response to different culture conditions, indicating the possible regulation of these genes in C. neogracile.

EST-based Identification of Genes Expressed in the Muscle of Olive Flounder, Paralichthys olivaceus

  • Park, Eun-Mi;Kim, Young-Ok;Nam, Bo-Hye;Kong, Hee Jeong;Kim, Woo-Jin;Lee, Sang-Jun;Choi, Tae-Jin
    • Journal of Marine Bioscience and Biotechnology
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    • v.2 no.3
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    • pp.168-173
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    • 2007
  • of expressed sequence tags (ESTs) is an efficient approach for gene discovery, expression profiling, and development of resources useful for functional genomics. To analyze the transcriptome of olive flounder, Paralichthys olivaceus, we have conducted EST analysis using cDNA libraries made from muscle of P. olivaceus. Redundant ESTs were assembled into overlapping contigs by using the assembly program ICAtools software. We found that the 221 ESTs were composed of 21 clusters and 35 singletons, suggesting that the overall redundancy of the library was 74.7%. Of the 221 clones, 218 clones (98.6%) were identified as known genes by BLAST searches and 3 clones (1.4%) did not match to any previously described genes. Based on major functions of their encoded proteins, the identified clones were classified into 13 broad categories. Sequence analysis of the ESTs revealed the presence of microsatellite-containing genes which may be valuable for further gene mapping studies. This study contributes to the identification of many EST clones that could be useful for genetics and developmental biology of olive flounder.

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Molecular Characterization of Neurally Differentiated Human Bone Marrow-derived Clonal Mesenchymal Stem Cells

  • Yi, TacGhee;Lee, Hyun-Joo;Cho, Yun-Kyoung;Jeon, Myung-Shin;Song, Sun U.
    • IMMUNE NETWORK
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    • v.14 no.1
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    • pp.54-65
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    • 2014
  • Bone marrow-derived mesenchymal stem cells (MSCs) are multipotent, with the ability to differentiate into different cell types. Additionally, the immunomodulatory activity of MSCs can downregulate inflammatory responses. The use of MSCs to repair injured tissues and treat inflammation, including in neuroimmune diseases, has been extensively explored. Although MSCs have emerged as a promising resource for the treatment of neuroimmune diseases, attempts to define the molecular properties of MSCs have been limited by the heterogeneity of MSC populations. We recently developed a new method, the subfractionation culturing method, to isolate homogeneous human clonal MSCs (hcMSCs). The hcMSCs were able to differentiate into fat, cartilage, bone, neuroglia, and liver cell types. In this study, to better understand the properties of neurally differentiated MSCs, gene expression in highly homogeneous hcMSCs was analyzed. Neural differentiation of hcMSCs was induced for 14 days. Thereafter, RNA and genomic DNA was isolated and subjected to microarray analysis and DNA methylation array analysis, respectively. We correlated the transcriptome of hcMSCs during neural differentiation with the DNA methylation status. Here, we describe and discuss the gene expression profile of neurally differentiated hcMSCs. These findings will expand our understanding of the molecular properties of MSCs and contribute to the development of cell therapy for neuroimmune diseases.

Analysis of Disease Progression-Associated Gene Expression Profile in Fibrillin-1 Mutant Mice: New Insight into Molecular Pathogenesis of Marfan Syndrome

  • Kim, Koung Li;Choi, Chanmi;Suh, Wonhee
    • Biomolecules & Therapeutics
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    • v.22 no.2
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    • pp.143-148
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    • 2014
  • Marfan syndrome (MFS) is a dominantly inherited connective tissue disorder caused by mutations in the gene encoding fibrillin-1 (FBN1) and is characterized by aortic dilatation and dissection, which is the primary cause of death in untreated MFS patients. However, disease progression-associated changes in gene expression in the aortic lesions of MFS patients remained unknown. Using a mouse model of MFS, FBN1 hypomorphic mouse (mgR/mgR), we characterized the aortic gene expression profiles during the progression of the MFS. Homozygous mgR mice exhibited MFS-like phenotypic features, such as fragmentation of elastic fibers throughout the vessel wall and were graded into mgR1-4 based on the pathological severity in aortic walls. Comparative gene expression profiling of WT and four mgR mice using microarrays revealed that the changes in the transcriptome were a direct reflection of the severity of aortic pathological features. Gene ontology analysis showed that genes related to oxidation/reduction, myofibril assembly, cytoskeleton organization, and cell adhesion were differentially expressed in the mgR mice. Further analysis of differentially expressed genes identified several candidate genes whose known roles were suggestive of their involvement in the progressive destruction of aorta during MFS. This study is the first genome-wide analysis of the aortic gene expression profiles associated with the progression of MFS. Our findings provide valuable information regarding the molecular pathogenesis during MFS progression and contribute to the development of new biomarkers as well as improved therapeutic strategies.

Transcriptome profile of one-month-old lambs' granulosa cells after superstimulation

  • Wu, Yangsheng;Lin, Jiapeng;Li, Xiaolin;Han, Bing;Wang, Liqin;Liu, Mingjun;Huang, Juncheng
    • Asian-Australasian Journal of Animal Sciences
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    • v.30 no.1
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    • pp.20-33
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    • 2017
  • Objective: Superstimulatory treatment of one-month-old lambs can achieve synchronous development of numerous growing follicles. However, these growing follicles cannot complete maturation and ovulation. Oocyte maturation and competence are acquired during follicular development, in which granulosa cells play an essential role. Methods: In this study, we applied RNA sequencing to analyze and compare gene expression between prepubertal and adult superstimulated follicle granulosa cells in sheep. Results: There were more than 300 genes that significantly differed in expression. Among these differently expressed genes, many extracellular matrix genes (EGF containing Fibulin Like Extracellular Matrix Protein 1, pentraxin 3, adrenomedullin, and osteopontin) were significantly down-regulated in the superstimulated follicles. Ingenuity pathway and gene ontology analyses revealed that processes of axonal guidance, cell proliferation and DNA replication were expressed at higher levels in the prepubertal follicles. Epidermal growth factor, T-Box protein 2 and beta-estradiol upstream regulator were predicted to be active in prepubertal follicles. By comparison, tumor protein P53 and let-7 were most active in adult follicles. Conclusion: These results may contribute to a better understanding of the mechanisms governing the development of granulosa cells in the growing follicle in prepubertal sheep.

Identification of piRNAs in Hela cells by massive parallel sequencing

  • Lu, Yilu;Li, Chao;Zhang, Kun;Sun, Huaqin;Tao, Dachang;Liu, Yunqiang;Zhang, Sizong;Ma, Yongxin
    • BMB Reports
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    • v.43 no.9
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    • pp.635-641
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    • 2010
  • Piwi proteins and Piwi-interacting RNAs (piRNAs) have been implicated in transposon control in germline from Drosophila to mammals. To examine the profile of small RNA expression in human cancer cells and explore difference in small RNA transcriptome, small RNA libraries prepared from wildtype, HILI overexpressed and HILI knockdowned Hela cells were sequenced using Solexa technology. piRNAs and other repeat-associated small RNAs were observed in Hela cells. By using in situ hybridization, piR-49322 was localized in the nucleolus and around the periphery of nuclear membrane in Hela cells. Following the overexpression of HILI, the retrotransposon elements LINE1 was significantly repressed, while LINE1-associated small RNAs decreased in abundance. The present study demonstrated that HILI along with piRNAs plays a role in LINE1 suppression in Hela cancer cell line.