• Title/Summary/Keyword: Epigenetic regulation

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Human Immunodeficiency Virus-l Tat Positively Regulates the Human CD99 Gene via DNA Demethylation (Human Immunodeficiency Virus-1 Tat 단백에 의한 인간 CD99유전자의 조절기전에 대한 연구)

  • Lee, Eu-Gene;Kim, Ye-Ri;Lee, Mi-Kyung;Lee, Im-Soon
    • Korean Journal of Microbiology
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    • v.44 no.4
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    • pp.277-281
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    • 2008
  • HIV affects many organ systems. Patients with HIV infection have substantially increased risk of developing various cancers, primarily by opportunistic infection with oncogenic viruses due to their immunocompromised status. However, extensive evidence also indicates that the viral protein, Tat itself, may playas a major factor in the development of AIDS-related neoplasms. The molecular mechanism underlying Tat's oncogenic activity may include deregulation of cellular genes. Therefore, in this study, we examined the effect of HIV-l Tat on CD99 as one of the target cellular genes, which is a well-known tumor marker in several cancers. By using established HeLa clones that are stably expressing Tat, we found that CD99 is upregulated by endogenous Tat, whereas STAT3 is down regulated. Upon the screening of genes differentially expressed between Tat-stable cells and the control cells by using the gene fishing technique, DEG, we detected 3 genes which expression is affected by the presence of Tat. Furthermore, the methylation specific PCR analysis of the stably Tat expressing cell lines revealed that the CD99 promoter is de methylated in the presence of Tat. Taken together, these results open a potential role of CD99 in AIDS-related oncogenesis via epigenetic regulation by HIV-1 Tat.

Biological Function and Structure of Transposable Elements (이동성 유전인자의 구조 및 생물학적 기능)

  • Kim, So-Won;Kim, Woo Ryung;Kim, Heui-Soo
    • Journal of Life Science
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    • v.29 no.9
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    • pp.1047-1054
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    • 2019
  • Transposable elements (TEs) occupy approximately 45% of the human genome and can enter functional genes randomly. During evolutionary radiation, multiple copies of TEs are produced by duplication events. Those elements contribute to biodiversity and phylogenomics. Most of them are controlled by epigenetic regulation, such as methylation or acetylation. Every species contains their own specific mobile elements, and they are divided into DNA transposons and retrotransposons. Retrotransposons can be divided by the presence of a long terminal repeat (LTR). They show various biological functions, such as promoter, enhancer, exonization, rearrangement, and alternative splicing. Also, they are strongly implicated to genomic instability, causing various diseases. Therefore, they could be used as biomarkers for the diagnosis and prognosis of diseases such as cancers. Recently, it was found that TEs could produce miRNAs, which play roles in gene inhibition through mRNA cleavage or translational repression, binding seed regions of target genes. Studies of TE-derived miRNAs offer a potential for the expression of functional genes. Comparative analyses of different types of miRNAs in various species and tissues could be of interest in the fields of evolution and phylogeny. Those events allow us to understand the importance of TEs in relation to biological roles and various diseases.

Roles of Local Estrogen and Progesterone Mediated Receptors in the Regulation of Endometrial Inflammation (자궁내막 염증에 대한 지엽적 에스트로겐 및 프로게스테론 매개 수용체의 역할)

  • Gyesik Min
    • Journal of Life Science
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    • v.33 no.1
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    • pp.102-113
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    • 2023
  • This review discusses the cellular and molecular mechanisms by which the endometrial estrogen and progesterone receptors regulate local estrogen production, expression of the specific estrogen receptors, progesterone resistance, inflammatory responses and the differentiation and survival of endometriotic cells in endometrial inflammation. The epigenetic aberrations of endometrial stromal cells play an important role in the pathogenesis and progression of endometriosis. In particular, differential methylation of the estrogen receptor genes changes in the stromal cells the dominancy of estrogen receptor from ERα into ERβ, and results in the abnormal estrogen responses including inflammation, progesterone resistance and the disturbance of retinoid synthesis. These stromal cells also stimulate local estrogen production in response to PGE2 and the SF-1 mediated induction of steroidogenic enzyme expression, and the increased estradiol then feeds back into the ERβ to repeat the vicious inflammatory cycle through the activation of COX-2. In addition, high levels of ERβ expression may also change the chromatin structure of endometrial mesenchymal stem cells, and together with the repeated menstrual cycles can induce formation of the endometriotic tissue. The cascade of these serial events then leads to cell adhesion, angiogenesis and survival of the differentiation-disregulated stromal cells through the action of inflammatory factors such as ERβ-mediated estrogen, TNF-α and TGF-β1. Therefore, understanding of the dynamic hormonal changes during the menstrual cycle and the corresponding signal transduction mechanisms of the related nuclear receptors in endometrium would provide new insights for treating inflammatory diseases such as the endometriosis.

Microbial short-chain fatty acids: a bridge between dietary fibers and poultry gut health - A review

  • Ali, Qasim;Ma, Sen;La, Shaokai;Guo, Zhiguo;Liu, Boshuai;Gao, Zimin;Farooq, Umar;Wang, Zhichang;Zhu, Xiaoyan;Cui, Yalei;Li, Defeng;Shi, Yinghua
    • Animal Bioscience
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    • v.35 no.10
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    • pp.1461-1478
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    • 2022
  • The maintenance of poultry gut health is complex depending on the intricate balance among diet, the commensal microbiota, and the mucosa, including the gut epithelium and the superimposing mucus layer. Changes in microflora composition and abundance can confer beneficial or detrimental effects on fowl. Antibiotics have devastating impacts on altering the landscape of gut microbiota, which further leads to antibiotic resistance or spread the pathogenic populations. By eliciting the landscape of gut microbiota, strategies should be made to break down the regulatory signals of pathogenic bacteria. The optional strategy of conferring dietary fibers (DFs) can be used to counterbalance the gut microbiota. DFs are the non-starch carbohydrates indigestible by host endogenous enzymes but can be fermented by symbiotic microbiota to produce short-chain fatty acids (SCFAs). This is one of the primary modes through which the gut microbiota interacts and communicate with the host. The majority of SCFAs are produced in the large intestine (particularly in the caecum), where they are taken up by the enterocytes or transported through portal vein circulation into the bloodstream. Recent shreds of evidence have elucidated that SCFAs affect the gut and modulate the tissues and organs either by activating G-protein-coupled receptors or affecting epigenetic modifications in the genome through inducing histone acetylase activities and inhibiting histone deacetylases. Thus, in this way, SCFAs vastly influence poultry health by promoting energy regulation, mucosal integrity, immune homeostasis, and immune maturation. In this review article, we will focus on DFs, which directly interact with gut microbes and lead to the production of SCFAs. Further, we will discuss the current molecular mechanisms of how SCFAs are generated, transported, and modulated the pro-and anti-inflammatory immune responses against pathogens and host physiology and gut health.

Lysine demethylase 3a in craniofacial and neural development during Xenopus embryogenesis

  • HYUN‑KYUNG LEE;TAYABA ISMAIL;CHOWON KIM;YOUNI KIM;JEEN‑WOO PARK;OH‑SHIN KWON;BEOM‑SIK KANG;DONG‑SEOK LEE;TAEJOON KWON;TAE JOO PARK;HYUN‑SHIK LEE
    • International Journal of Molecular Medicine
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    • v.43 no.2
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    • pp.1105-1113
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    • 2019
  • Epigenetic modifier lysine demethylase 3a (Kdm3a) specifically demethylates mono- and di-methylated ninth lysine of histone 3 and belongs to the Jumonji domain-containing group of demethylases. Kdm3a serves roles during various biological and pathophysiological processes, including spermatogenesis and metabolism, determination of sex, androgen receptor-mediated transcription and embryonic carcinoma cell differentiation. In the present study, physiological functions of Kdm3a were evaluated during embryogenesis of Xenopus laevis. Spatiotemporal expression pattern indicated that kdm3a exhibited its expression from early embryonic stages until tadpole stage, however considerable increase of kdm3a expression was observed during the neurula stage of Xenopus development. Depleting kdm3a using kdm3a antisense morpholino oligonucleotides induced anomalies, including head deformities, small-sized eyes and abnormal pigmentation. Whole-mount in situ hybridization results demonstrated that kdm3a knockdown was associated with defects in neural crest migration. Further, quantitative polymerase chain reaction revealed abnormal expression of neural markers in kdm3a morphants. RNA sequencing of kdm3a morphants indicated that kdm3a was implicated in mesoderm formation, cell adhesion and metabolic processes of embryonic development. In conclusion, the results of the present study indicated that Kdm3a may serve a role in neural development during Xenopus embryogenesis and may be targeted for treatment of developmental disorders. Further investigation is required to elucidate the molecular mechanism underlying the regulation of neural development by Kdm3a.