• Title/Summary/Keyword: transcriptional reprogramming

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Acceleration of Mesenchymal-to-Epithelial Transition (MET) during Direct Reprogramming Using Natural Compounds

  • Seo, Ji-Hye;Jang, Si Won;Jeon, Young-Joo;Eun, So Young;Hong, Yean Ju;Do, Jeong Tae;Chae, Jung-il;Choi, Hyun Woo
    • Journal of Microbiology and Biotechnology
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    • v.32 no.10
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    • pp.1245-1252
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    • 2022
  • Induced pluripotent stem cells (iPSCs) can be generated from somatic cells using Oct4, Sox2, Klf4, and c-Myc (OSKM). Small molecules can enhance reprogramming. Licochalcone D (LCD), a flavonoid compound present mainly in the roots of Glycyrrhiza inflata, acts on known signaling pathways involved in transcriptional activity and signal transduction, including the PGC1-α and MAPK families. In this study, we demonstrated that LCD improved reprogramming efficiency. LCD-treated iPSCs (LCD-iPSCs) expressed pluripotency-related genes Oct4, Sox2, Nanog, and Prdm14. Moreover, LCD-iPSCs differentiated into all three germ layers in vitro and formed chimeras. The mesenchymal-to-epithelial transition (MET) is critical for somatic cell reprogramming. We found that the expression levels of mesenchymal genes (Snail2 and Twist) decreased and those of epithelial genes (DSP, Cldn3, Crb3, and Ocln) dramatically increased in OR-MEF (OG2+/+/ROSA26+/+) cells treated with LCD for 3 days, indicating that MET effectively occurred in LCD-treated OR-MEF cells. Thus, LCD enhanced the generation of iPSCs from somatic cells by promoting MET at the early stages of reprogramming.

Transcriptional regulatory network during development in the olfactory epithelium

  • Im, SeungYeong;Moon, Cheil
    • 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.

The Ralstonia pseudosolanacearum Type III Effector RipL Delays Flowering and Promotes Susceptibility to Pseudomonas syringae in Arabidopsis thaliana

  • Wanhui Kim;Hyelim Jeon;Hyeonjung Lee;Kee Hoon Sohn;Cecile Segonzac
    • Molecules and Cells
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    • v.46 no.11
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    • pp.710-724
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    • 2023
  • The plant defense responses to microbial infection are tightly regulated and integrated with the developmental program for optimal resources allocation. Notably, the defense-associated hormone salicylic acid (SA) acts as a promoter of flowering while several plant pathogens actively target the flowering signaling pathway to promote their virulence or dissemination. Ralstonia pseudosolanacearum inject tens of effectors in the host cells that collectively promote bacterial proliferation in plant tissues. Here, we characterized the function of the broadly conserved R. pseudosolanacearum effector RipL, through heterologous expression in Arabidopsis thaliana. RipL-expressing transgenic lines presented a delayed flowering, which correlated with a low expression of flowering regulator genes. Delayed flowering was also observed in Nicotiana benthamiana plants transiently expressing RipL. In parallel, RipL promoted plant susceptibility to virulent strains of Pseudomonas syringae in the effector-expressing lines or when delivered by the type III secretion system. Unexpectedly, SA accumulation and SA-dependent immune signaling were not significantly affected by RipL expression. Rather, the RNA-seq analysis of infected RipL-expressing lines revealed that the overall amplitude of the transcriptional response was dampened, suggesting that RipL could promote plant susceptibility in an SA-independent manner. Further elucidation of the molecular mechanisms underpinning RipL effect on flowering and immunity may reveal novel effector functions in host cells.

Plant Exocytic Secretion of Toxic Compounds for Defense

  • Kwon, Chian;Yun, Hye Sup
    • Toxicological Research
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    • v.30 no.2
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    • pp.77-81
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    • 2014
  • In contrast to animals, plants do not have a circulatory system as well as mobile immune cells that allow them to protect themselves against pathogens. Instead, plants exclusively depend on the innate immune system to defend against pathogens. As typically observed in the animal innate immunity, plant immune responses are composed of pathogen detection, defense signaling which includes transcriptional reprogramming, and secretion of antimicrobial compounds. Although knowledge on recognition and subsequent signaling of pathogen-derived molecules called elicitors is now expanding, the mechanisms of how these immune molecules are excreted are yet poorly understood. Therefore, current understandings of how plants secrete defense products especially via exocytosis will be discussed in this review.

Reorganization of Chromatin Conformation from an Active to an Inactive State After Cessation of Transcription

  • Lee, Myeong-Sok
    • Journal of Microbiology
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    • v.34 no.1
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    • pp.54-60
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    • 1996
  • Taking advantage of the heat inducible HSP82 gene in yeast, chromatin structure after transcription cessation was investigated. Alteration of chromating conformation within the HSP82 gene transcription unit into an active state has been shown to correlate with its transcriptional induction. It was thus of interest to examine whether the active chromatin state within the HSP82 mRNA analysis, the gene ceased its transcription within a few hours of cultivation at a normal condition after heat induction. In this condition, an active chromatin conformation in the HSP82 gene body was changed into an inactie state which was revealed by DNase I resistance and by typical nucleosomal cutting periodicity in the corresponding chromatin. These results thus ruled out the possibility of a long-term maintenance of the DNase I sensitive chromatin after transcription cessation. DNA replication may be a critical event for the chromatin reprogramming.

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cDNA Microarray Analysis of Transcriptional Response to Hyperin in Human Gastric Cancer Cells

  • Jeoung, Dooil;Kim, Jae-Hwan;Lee, Youn-Hyung;Myungin Baek;Lee, Seongeun;Baek, Nam-In;Kim, Hae-Yeong
    • Journal of Microbiology and Biotechnology
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    • v.12 no.4
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    • pp.664-668
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    • 2002
  • Antioxidants either scavenge superoxide and free radicals or stimulate the detoxification mechanisms within cells, resulting in increased detoxification of free radicals formation. Hyperin, isolated from the stem of Uncaria rhynchophylla, prevented oxygen radical formation and inhibited lipid oxidation. The effective concentrations were 31.3 $\mu$M for a radical scavenging assay and 2.2 $\mu$M for a microsome assay. cDNA microarray analysis to determine which genes were modulated by hyperin found that 50 genes were upregulated and 37 genes were downregulated in SNU-668 human gastric cancer cells. Among these genes, thirteen genes that were significantly affected by hyperin were verified by RT-PCR for their effect of genetic reprogramming.

Mitochondrial defect-responsive gene signature in liver-cancer progression

  • Lee, Young-Kyoung;Woo, Hyun Goo;Yoon, Gyesoon
    • BMB Reports
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    • v.48 no.11
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    • pp.597-598
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    • 2015
  • Mitochondrial respiratory defect is a key bioenergetics feature of hepatocellular carcinoma (HCC) cells. However, their involvement and roles in HCC development and progression remain unclear. Recently, we identified 10 common mitochondrial defect (CMD) signature genes that may be induced by retrograde signaling-mediated transcriptional reprogramming in response to HCC mitochondrial defects. HCC patients with enriched expression of these genes had poor prognostic outcomes, such as shorter periods of overall survival and recurrence-free survival. Nuclear protein 1 (NUPR1), a key transcription regulator, was up-regulated by Ca++-mediated retrograde signaling. NUPR1-centric network analysis and a biochemical promoter-binding assay demonstrated that granulin (GRN) is a key downstream effector of NUPR1 for the regulation of HCC cell invasiveness; association analysis of the NUPR1-GRN pathway supported this conclusion. Mitochondrial respiratory defects and retrograde signaling thus play pivotal roles in HCC progression, highlighting the potential of the NUPR1-GRN axis as a novel diagnostic marker and therapeutic target for HCC.

HDAC4 Regulates Muscle Fiber Type-Specific Gene Expression Programs

  • Cohen, Todd J.;Choi, Moon-Chang;Kapur, Meghan;Lira, Vitor A.;Yan, Zhen;Yao, Tso-Pang
    • Molecules and Cells
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    • v.38 no.4
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    • pp.343-348
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    • 2015
  • Fiber type-specific programs controlled by the transcription factor MEF2 dictate muscle functionality. Here, we show that HDAC4, a potent MEF2 inhibitor, is predominantly localized to the nuclei in fast/glycolytic fibers in contrast to the sarcoplasm in slow/oxidative fibers. The cytoplasmic localization is associated with HDAC4 hyper-phosphorylation in slow/oxidative-fibers. Genetic reprogramming of fast/glycolytic fibers to oxidative fibers by active CaMKII or calcineurin leads to increased HDAC4 phosphorylation, HDAC4 nuclear export, and an increase in markers associated with oxidative fibers. Indeed, HDAC4 represses the MEF2-dependent, PGC-$1{\alpha}$-mediated oxidative metabolic gene program. Thus differential phosphorylation and localization of HDAC4 contributes to establishing fiber type-specific transcriptional programs.

Temporal Expression of RNA Polymerase II in Porcine Oocytes and Embryos

  • Oqani, Reza;Lee, Min Gu;Tao, Lin;Jin, Dong Il
    • Reproductive and Developmental Biology
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    • v.36 no.4
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    • pp.237-241
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    • 2012
  • Embryonic genome activation (EGA) is the first major transition that occurs after fertilization, and entails a dramatic reprogramming of gene expression that is essential for continued development. Although it has been suggested that EGA in porcine embryos starts at the four-cell stage, recent evidence indicates that EGA may commence even earlier; however, the molecular details of EGA remain incompletely understood. The RNA polymerase II of eukaryotes transcribes mRNAs and most small nuclear RNAs. The largest subunit of RNA polymerase II can become phosphorylated in the C-terminal domain. The unphosphorylated form of the RNA polymerase II largest subunit C-terminal domain (IIa) plays a role in initiation of transcription, and the phosphorylated form (IIo) is required for transcriptional elongation and mRNA splicing. In the present study, we explored the nuclear translocation, nuclear localization, and phosphorylation dynamics of the RNA polymerase II C-terminal domain in immature pig oocytes, mature oocytes, two-, four-, and eight-cell embryos, and the morula and blastocyst. To this end, we used antibodies specific for the IIa and IIo forms of RNA polymerase II to stain the proteins. Unphosphorylated RNA polymerase II stained strongly in the nuclei of germinal vesicle oocytes, whereas the phosphorylated form of the enzyme was confined to the chromatin of prophase I oocytes. After fertilization, both unphosphorylated and phosphorylated RNA polymerase II began to accumulate in the nuclei of early stage one-cell embryos, and this pattern was maintained through to the blastocyst stage. The results suggest that both porcine oocytes and early embryos are transcriptionally competent, and that transcription of embryonic genes during the first three cell cycles parallels expression of phosphorylated RNA polymerase II.

Silica Nanoparticles Suppress the Root Rot of Panax ginseg from Ilyonectria mors-panacis Infection by Reducing Sugar Efflux into Apoplast

  • Abbai, Ragavendran;Ahn, Jong-Chan;Mohanan, Padmanaban;Mathiyalagan, Ramya;Gokulanathan, Anandapadmanaban;Kim, Yu-Jin;Kim, Yoen-Ju;Yang, Deok-Chun
    • Proceedings of the Plant Resources Society of Korea Conference
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    • 2018.04a
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    • pp.59-59
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    • 2018
  • Panax ginseng Meyer (Korean ginseng) is in the spotlight of Oriental medicine and is proclaimed as the king of medicinal plants owing to its adaptogenic characteristics. Ginseng root rot is a devastating disease caused by the fungus, Ilyonectria mors-panacis that generally attacks younger roots (~2 years), leading to defects in root quality, ginsenoside accumulation and also life cycle of the plant. Hence, there is an indispensable need to develop strategies resulting in tolerance against ginseng root rot. In the present study, we evaluated the effect of silica nanoparticles(N-SiO2) in Panax ginseng during I. mors-panacis infection. Long term analysis (30 dpi) revealed a striking 50% reduction in disease severity index upon 1mM and 2mM treatment of N-SiO2. However, N-SiO2 did not have any direct antifungal activity against I. mors-panacis. Membrane bound sugar efflux transporter, SWEET (Sugars Will Eventually be Exported Transporters) was identified in ginseng and as expected, its expression was suppressed upon N-SiO2 treatment in the root rot pathosystem. Furthermore, the total and reducing sugars in the apoplastic fluid clearly revealed that N-SiO2 regulates sugar efflux into apoplast. In a nut shell, N-SiO2 administration induces transcriptional reprogramming in ginseng roots, leading to regulated sugar efflux into apoplast resulting in enhanced tolerance against I. mors-panacis.

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