• Title/Summary/Keyword: genetic regulation

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Regulation of Pluripotency-related Genes and Differentiation in Mouse Embryonic Stem Cells by Direct Delivery of Cell-penetrating Peptide-conjugated CARM1 Recombinant Protein

  • Choi, Sara;Jo, Junghyun;Seol, Dong-Won;Cha, Soo Kyung;Lee, Jeoung Eun;Lee, Dong Ryul
    • Development and Reproduction
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    • v.17 no.1
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    • pp.9-16
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    • 2013
  • Coactivator-associated arginine methyltransferase 1 (CARM1) is included in the protein arginine methyltransferase (PRMT) family, which methylates histone arginine residues through posttranslational modification. It has been proposed that CARM1 may up-regulate the expression of pluripotency-related genes through the alteration of the chromatin structure. Mouse embryonic stem cells (mESCs) are pluripotent and have the ability to self-renew. The cells are mainly used to study the genetic function of novel genes, because the cells facilitate the transmission of the manipulated genes into target mice. Since the up-regulated methylation levels of histone arginine residue lead to the maintenance of pluripotency in embryos and stem cells, it may be suggested that CARM1 overexpressing mESCs elevate the expression of pluripotency-related genes in reconstituted embryos for transgenic mice and may resist the differentiation into trophectoderm (TE). We constructed a fusion protein by connecting CARM1 and 7X-arginine (R7). As a cell-penetrating peptide (CPP), can translocate CARM1 protein into mESCs. CPP-CARM1 protein was detected in the nuclei of the mESCs after a treatment of 24 hours. Accordingly, the expression of pluripotency-related genes was up-regulated in CPP-CARM1-treated mESCs. In addition, CPP-CARM1-treated mESC-derived embryoid bodies (EBs) showed an elevated expression of pluripotency-related genes and delayed spontaneous differentiation. This result suggests that the treatment of recombinant CPP-CARM1 protein elevates the expression of pluripotency-related genes of mESCs by epigenetic modification, and this protein-delivery system could be used to modify embryonic fate in reconstituted embryos with mESCs.

Loss of Hfe Function Reverses Impaired Recognition Memory Caused by Olfactory Manganese Exposure in Mice

  • Ye, Qi;Kim, Jonghan
    • Toxicological Research
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    • v.31 no.1
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    • pp.17-23
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    • 2015
  • Excessive manganese (Mn) in the brain promotes a variety of abnormal behaviors, including memory deficits, decreased motor skills and psychotic behavior resembling Parkinson's disease. Hereditary hemochromatosis (HH) is a prevalent genetic iron overload disorder worldwide. Dysfunction in HFE gene is the major cause of HH. Our previous study has demonstrated that olfactory Mn uptake is altered by HFE deficiency, suggesting that loss of HFE function could alter manganese-associated neurotoxicity. To test this hypothesis, Hfe-knockout ($Hfe^{-/-}$) and wild-type ($Hfe^{+/+}$) mice were intranasally-instilled with manganese chloride ($MnCl_2$ 5 mg/kg) or water daily for 3 weeks and examined for memory function. Olfactory Mn diminished both short-term recognition and spatial memory in $Hfe^{+/+}$ mice, as examined by novel object recognition task and Barnes maze test, respectively. Interestingly, $Hfe^{-/-}$ mice did not show impaired recognition memory caused by Mn exposure, suggesting a potential protective effect of Hfe deficiency against Mn-induced memory deficits. Since many of the neurotoxic effects of manganese are thought to result from increased oxidative stress, we quantified activities of anti-oxidant enzymes in the prefrontal cortex (PFC). Mn instillation decreased superoxide dismutase 1 (SOD1) activity in $Hfe^{+/+}$ mice, but not in $Hfe^{-/-}$ mice. In addition, Hfe deficiency up-regulated SOD1 and glutathione peroxidase activities. These results suggest a beneficial role of Hfe deficiency in attenuating Mn-induced oxidative stress in the PFC. Furthermore, Mn exposure reduced nicotinic acetylcholine receptor levels in the PFC, indicating that blunted acetylcholine signaling could contribute to impaired memory associated with intranasal manganese. Together, our model suggests that disrupted cholinergic system in the brain is involved in airborne Mn-induced memory deficits and loss of HFE function could in part prevent memory loss via a potential up-regulation of anti-oxidant enzymes in the PFC.

Lipooligosaccharide biosynthesis genes of nontypable Haemophilus influenzae 2019

  • Lee, Na-Gyong;Melvin G. Sunshine;Jeffery J. Engstrom;Bradford W. Gibson;Michael A. Apicella
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 1996.11a
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    • pp.65-73
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    • 1996
  • LPS/LOS, the compound found only in gram-negative bacterial outer membrane, plays important roles in bacterial maintenance as well as its pathogenesis. We isolated and characterized several genes required for NTHi 2019 LOS biosynthesis, which encode enzymes required for sugar substrate synthesis or the transfer of substrates to receptor molecules. The htrB gene, however, appears to have more complex role. It has acryltransferase activity as well as various other activity, which may control regulation of LOS biosynthesis as well as its pathogenicity. Evidences supporting the latter come from the observations that the lipid A of the B29 induced significantly less TNF ${\alpha}$ from macrophages than that of the wild type LOS (unpublished data). H. influenzae A2-htrB mutant strain was also significantly less invasive than the wild type strain. The structural similarities of the enterobacterial LPS and the Haemophilus LOS enabled us to isolate the NTHi 2019 genes involved in LOS biosynthesis genes by using the S. typhimurium LPS deep core mutants. While a similar approach has been used for E. coli, this technique for selection of an LPS phenotype has not been applied to nonenterobacterial species. The difficulties inherent in the molecular manipulation of organism such as Neisseria and Haemophilus species make this approach particularly attractive in the identification and cloning LOS genes. Studies on genetic features of LPS/LOS biosynthesis would be useful for understanding bacterial pathogenesis as well as for developing vaccines for these gram-negative pathogenic bacteria.

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Current status on expression profiling using rice microarray (벼 microarray를 이용한 유전자발현 profiling 연구동향)

  • Yoon, Ung-Han;Kim, Yeon-Ki;Kim, Chang-Kug;Hahn, Jang-Ho;Kim, Dong-Hern;Lee, Tae-Ho;Lee, Gang-Seob;Park, Soo-Chul;Nahm, Baek-Hie
    • Journal of Plant Biotechnology
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    • v.37 no.2
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    • pp.144-152
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    • 2010
  • As the International Rice Genome Sequencing Project (IRGSP) was completed in 2005 and opened to the public, many countries are making a lot of investments in researches on the utilization of sequence information along with system development. Also, the necessity of the functional genomics researches using microarray is increased currently to secure unique genes related with major agricultural traits and analyze metabolic pathways. Microrarray enables efficient analysis of large scale gene expression and related transcription regulation. This review aims to introduce available microarrays made based on rice genome information and current status of gene expression analysis using these microarrays integrated with the databases available to the public. Also, we introduce the researches on the large scale functional analysis of genes related with useful traits and genetic networks. Understanding of the mechanism related with mutual interaction between proteins with co-expression among rice genes can be utilized in the researches for improving major agricultural traits. The direct and indirect interactions of various genes would provide new functionality of rice. The recent results of the various expression profiling analysis in rice will promote functional genomic researches in plants including rice and provide the scientists involved in applications researches with wide variety of expression informations.

RNA Binding Proteins and its Regulation of Gene Expression (RNA 결합 단백질과 유전자 발현조절)

  • Roh, Kyung Hee;Kang, Han-Chul;Kim, Jong-Bum;Kim, Hyun-UK;Lee, Kyung-Ryeol;Kim, Sun Hee
    • Journal of Applied Biological Chemistry
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    • v.58 no.3
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    • pp.201-208
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    • 2015
  • The role of RNA-binding proteins (RBPs) to regulate expression of genes seems to be very important. RBPs play important roles in RNA related bioprocess such as transcription, pre-mRNA splicing, polyadenylation, transport, localization, translation, turn over and maintenance of structure. Despite of many researches on RNA binding proteins, detailed mechanisms of these proteins have not been fully understood. It seems that many parts of RBPs remains unknown and should be characterized for the better understanding of gene expression. Recently, genetic, biochemical, and bioinformatic analysis of genomes revealed a vast array of RBPs and many parts are interesting to understand bioprocessing including gene expression.

Utilization of Soil Resources for Maximum Production of Food Grains (식량 최대생산을 위한 토양자원 이용)

  • Sin Je Seong;Kim Lee Yeol
    • Proceedings of the Korean Society of Crop Science Conference
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    • 1999.11a
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    • pp.145-167
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    • 1999
  • Our self-sufficiency of food has become less than $30{\%}$ and our nation is highly dependant on world's grain market for food. which is unstable in long term due to the world population growth faster than food production. Therefore, it is a great possibility that food might become a political weapon by way of its global shortage. its purchasing difficulty in international free trade market. and the resultant price rising. Our maximal capability of food production has become the most outstanding problem in the dimension of future food security. It would be the utmost scheme for maximal production of food to realize the maximal utilization of arable land through the enlargement of sufficient farming land and the conversion of rotation system for the more grain production. Extensional enlargement of arable land can be positively executed through the development of farming land in domestic and abroad countries. The readjustment of arable land and the installation or irrigation and drainage system can enforce the farming basement for maximal utilization of arable land through the improved rotation between paddy and upland. The prevention policy against farming land encroachment should be strictly executed through grain production encouragement on resting or marginal lands and regulation of utilization conversion for the other than food production on high grade farming lands. It is also required urgently to develope high yielding and high quality varieties through advanced genetic technology for the improvement of unit area yield, especially of wheat, corn. and soybean we import in large quantity The maximal utilization of arable land for the highest production of food can be realized through rational rotation system, the most adaptable crop cultivation on the suitable land, and the most optimal fertilization through the GIS analysis of agricultural environment information on the basis of the computerized soil resource data on super detailed soil maps(1:5000) surveyed plot by plot of whole nation.

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IDENTIFICATION OF GENES EXPRESSED IN LOW-DOSE-RATE γ-IRRADIATED MOUSE WHOLE BRAIN

  • Bong, Jin Jong;Kang, Yu Mi;Choi, Seung Jin;Kim, Dong-Kwon;Lee, Kyung Mi;Kim, Hee Sun
    • Journal of Radiation Protection and Research
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    • v.38 no.4
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    • pp.166-171
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    • 2013
  • While high-dose ionizing radiation results in long term cellular cytotoxicity, chronic low-dose (<0.2 Gy) of X- or ${\gamma}$-ray irradiation can be beneficial to living organisms by inducing radiation hormesis, stimulating immune function, and adaptive responses. During chronic low-dose-rate radiation (LDR) exposure, whole body of mice is exposed to radiation, however, it remains unclear if LDR causes changes in gene expression of the whole brain. Therefore, we aim to investigate expressed genes (EGs) and signaling pathways specifically regulated by LDR-irradiation ($^{137}Cs$, a cumulative dose of 1.7 Gy for total 100 days) in the whole brain. Using microarray analysis of whole brain RNA extracts harvested from ICR and AKR/J mice after LDR-irradiation, we discovered that two mice strains displayed distinct gene regulation patterns upon LDR-irradiation. In ICR mice, genes involved in ion transport, transition metal ion transport, and developmental cell growth were turned on while, in AKR/J mice, genes involved in sensory perception, cognition, olfactory transduction, G-protein coupled receptor pathways, inflammatory response, proteolysis, and base excision repair were found to be affected by LDR. We validated LDR-sensitive EGs by qPCR and confirmed specific upregulation of S100a7a, Olfr624, and Gm4868 genes in AKR/J mice whole brain. Therefore, our data provide the first report of genetic changes regulated by LDR in the mouse whole brain, which may affect several aspects of brain function.

Review on Predictors of Weight Loss Maintenance after Successful Weight Loss in Obesity Treatment (비만치료에 있어서 감량 후 체중 유지에 영향을 주는 요인에 관한 고찰)

  • Kwon, Yu-Kyung;Kim, Seo-Young;Lim, Young-Woo;Park, Young-Bae
    • Journal of Korean Medicine for Obesity Research
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    • v.19 no.2
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    • pp.119-136
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    • 2019
  • Objectives: People often fail to maintain their weight even though they have succeeded in weight loss. The purpose of this study was to review previously published study results with regards to the predictive factors associated with weight loss maintenance after successful weight loss. Methods: The authors searched for the articles related to weight loss maintenance after successful weight loss, published up until June 2019 on PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), Embase, Research Information Sharing Service (RISS), and Koreanstudies Information Service System (KISS). A total of 76 articles were finally selected. From the study results, changeable and unchangeable predictors were extracted, and these predictors were examined according to detailed categories. Results: The changeable predictors of weight loss maintenance included behavioral factors, psychological factors and treatment process-related factors, whereas the unchangeable predictors included genetic and physiological factors, demographic factors, history of treatment on obesity-related factors. The main factors of weight loss maintenance were changeable predictors such as healthy eating habits, dietary intake control, binge eating control, regular exercise and physical activity, depression and stress control, social supports, self-regulation, self-weighing and initial weight loss and unchangeable predictors such as low initial weight and maximum lifetime weight. Conclusions: The results of our review results suggest that changeable and unchangeable predictors of weight loss maintenance should be carefully examined during treatments of obesity.

Critical Role of the Cysteine 323 Residue in the Catalytic Activity of Human Glutamate Dehydrogenase Isozymes

  • Yang, Seung-Ju;Cho, Eun Hee;Choi, Myung-Min;Lee, Hyun-Ju;Huh, Jae-Wan;Choi, Soo Young;Cho, Sung-Woo
    • Molecules and Cells
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    • v.19 no.1
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    • pp.97-103
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    • 2005
  • The role of residue C323 in catalysis by human glutamate dehydrogenase isozymes (hGDH1 and hGDH2) was examined by substituting Arg, Gly, Leu, Met, or Tyr at C323 by cassette mutagenesis using synthetic human GDH isozyme genes. As a result, the $K_m$ of the enzyme for NADH and ${\alpha}-ketoglutarate$ increased up to 1.6-fold and 1.1-fold, respectively. It seems likely that C323 is not responsible for substrate-binding or coenzyme-binding. The efficiency ($k_{cat}/K_m$) of the mutant enzymes was only 11-14% of that of the wild-type isozymes, mainly due to a decrease in $k_{cat}$ values. There was a linear relationship between incorporation of [$^{14}C$]p-chloromercuribenzoic acid and loss of enzyme activity that extrapolated to a stoichiometry of one mol of [$^{14}C$] incorporated per mol of monomer for wild type hGDHs. No incorporation of [$^{14}C$]p-chloromercuribenzoic acid was observed with the C323 mutants. ADP and GTP had no effect on the binding of p-chloromercuribenzoic acid, suggesting that C323 is not directly involved in allosteric regulation. There were no differences between the two hGDH isozymes in sensitivities to mutagenesis at C323. Our results suggest that C323 plays an important role in catalysis by human GDH isozymes.

High-Throughput In Vitro Screening of Changed Algal Community Structure Using the PhotoBiobox

  • Cho, Dae-Hyun;Cho, Kichul;Heo, Jina;Kim, Urim;Lee, Yong Jae;Choi, Dong-Yun;Yoo, Chan;Kim, Hee-Sik;Bae, Seunghee
    • Journal of Microbiology and Biotechnology
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    • v.30 no.11
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    • pp.1785-1791
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    • 2020
  • In a previous study, the sequential optimization and regulation of environmental parameters using the PhotoBiobox were demonstrated with high-throughput screening tests. In this study, we estimated changes in the biovolume-based composition of a polyculture built in vitro and composed of three algal strains: Chlorella sp., Scenedesmus sp., and Parachlorella sp. We performed this work using the PhotoBiobox under different temperatures (10-36℃) and light intensities (50-700 μmol m-2 s-1) in air and in 5% CO2. In 5% CO2, Chlorella sp. exhibited better adaptation to high temperatures than in air conditions. Pearson's correlation analysis showed that the composition of Parachlorella sp. was highly related to temperature whereas Chlorella sp. and Scenedesmus sp. showed negative correlations in both air and 5% CO2. Furthermore, light intensity slightly affected the composition of Scenedesmus sp., whereas no significant effect was observed in other species. Based on these results, it is speculated that temperature is an important factor in influencing changes in algal polyculture community structure (PCS). These results further confirm that the PhotoBiobox is a convenient and available tool for performance of lab-scale experiments on PCS changes. The application of the PhotoBiobox in PCS studies will provide new insight into polyculture-based ecology.