• Clinical and Experimental Reproductive Medicine
• /
• 제43권2호
• /
• pp.82-89
• /
• 2016

Objective: The long interspersed elements (LINE-1, L1s) are a group of genetic elements found in large numbers in the human genome that can translate into phenotype by controlling genes. Growing evidence supports the role of epigenetic in polycystic ovary syndrome (PCOS). The purpose of this study is to evaluate the DNA methylation levels in LINE-1 in a tissue-specific manner using cumulus cells from patients with PCOS compared with normal controls. Methods: The study included 19 patients with PCOS and 22 control patients who were undergoing controlled ovarian hyperstimulation. After oocyte retrieval, cumulus cells were extracted. LINE-1 DNA methylation levels were analysed by bisulfite treatment, polymerase chain reaction, and restriction enzyme digestion. The Connection Up- and Down-Regulation Expression Analysis of Microarrays software package was used to compare the gene regulatory functions of intragenic LINE-1. Results: The results showed higher LINE-1 DNA methylation levels in the cumulus cells of mature oocytes in PCOS patients, 79.14 (${\pm}2.66$) vs. 75.40 (${\pm}4.92$); p=0.004, but no difference in the methylation of cumulus cells in immature oocytes between PCOS and control patients, 70.33 (${\pm}4.79$) vs. 67.79 (${\pm}5.17$); p=0.155. However, LINE-1 DNA methylation levels were found to be higher in the cumulus cells of mature oocytes than in those of immature oocytes in both PCOS and control patients. Conclusion: These findings suggest that the epigenetic modification of LINE-1 DNA may play a role in regulating multiple gene expression that affects the pathophysiology and development of mature oocytes in PCOS.

• 생명과학회지
• /
• 제31권11호
• /
• pp.995-1003
• /
• 2021

크로마틴 리모델링은 후성유전기전을 통해 유전자 발현을 조절한다. 비정상적인 히스톤 변형이 우울증 발생에 관여하는 것으로 알려져 있다. p11 (S100A10)은 인간과 설치류에서 우울증의 병태생리에 관여한다고 보고되었다. 본 연구는 우울증 동물모델인 장기간 예측 불가능한 스트레스가 마우스 해마에서 p11 유전자 promoter의 히스톤 변형에 미치는 영향을 조사하고자 하였다. C57BL/6 마우스에 21일 동안 스트레스를 가하고, 강제수영검사를 수행하여 우울 유사 행동 양상을 측정하였다. Real time PCR 및 Western blotting 분석법으로 p11 발현 변화를 조사하였으며, 염색질 면역침전분석법을 수행하여 p11 promoter의 히스톤 H3 아세틸화 및 메틸화 양을 측정하였다. 장기간 예측 불가능한 스트레스는 강제수영검사에서 부동시간을 증가시켜 우울 유사 행동을 나타내었으며, 해마의 p11 mRNA 및 단백질 발현을 유의하게 감소시켰다. 또한 p11 promoter의 히스톤 H3 아세틸화(Ac-H3) 및 H3-K4 트리메틸화(H3K4met3)를 유의하게 감소시켰으며, H3-K27 트리메틸화(H3K27met3)를 증가시켰다. 본 연구결과는 만성 스트레스가 해마에서 p11 유전자의 후성유전적 억제를 야기하여 p11 유전자의 발현을 감소시킴을 시사한다.

• BMB Reports
• /
• 제47권8호
• /
• pp.424-432
• /
• 2014

The defining feature of Parkinson's disease is a progressive and selective demise of dopaminergic neurons. A recent report on Parkinson's disease animal model demonstrates that poly (ADP-ribose) (PAR) dependent cell death, also named parthanatos, is accountable for selective dopaminergic neuronal loss. Parthanatos is a programmed necrotic cell death, characterized by PARP1 activation, apoptosis inducing factor (AIF) nuclear translocation, and large scale DNA fragmentation. Besides cell death regulation via interaction with AIF, PAR molecule mediates diverse cellular processes including genomic stability, cell division, transcription, epigenetic regulation, and stress granule formation. In this review, we will discuss the roles of PARP1 activation and PAR molecules in the pathological processes of Parkinson's disease. Potential interaction between PAR molecule and Parkinson's disease protein interactome are briefly introduced. Finally, we suggest promising points of therapeutic intervention in the pathological PAR signaling cascade to halt progression in Parkinson's disease.

• Asian Pacific Journal of Cancer Prevention
• /
• 제15권3호
• /
• pp.1403-1410
• /
• 2014

Epigenetic regulators like histone deacetylases (1 and 2), and viral onco-proteins (E6/E7) are known to be overexpressed in cervical cancer cells. The present study was designed to investigate the effect of curcumin on HDACs (1 and 2) and HPV E6/E7 in the cervical cancer cell line SiHa and a drug resistant clone $SiHa^R$ (derived from SiHa). It was further intended to investigate whether curcumin could sensitize the cells towards cisplatin induced cell killing by modulation of multi drug resistant proteins like MRP1 and Pgp1. Curcumin inhibited HDACs, HPV expression and differentially increased acetylation and up-regulation of p53 in SiHa and $SiHa^R$, leading to cell cycle arrest at G1-S phase. Up-regulation of pRb, p21, p27 and corresponding inhibition of cyclin D1 and CDK4 were observed. Cisplatin resistance in $SiHa^R$ due to over-expression of MRP1 and Pgp1 was overcome by curcumin. Curcumin also sensitized both the cervical cancer cells towards cisplatin induced cell killing. Inhibition of HDACs and HPVs led to cell cycle arrest at G1/S phase by alteration of cell cycle regulatory proteins. Suppression of MRP1 and Pgp1 by curcumin resulted in sensitization of cervical cancer cells, lowering the chemotherapeutic dose of the drug cisplatin.

• BMB Reports
• /
• 제51권6호
• /
• pp.280-289
• /
• 2018

Previously considered as a component of transcriptional noise, long noncoding RNAs (lncRNAs) were neglected as a therapeutic target, however, recently increasing evidence has shown that lncRNAs can participate in numerous biological processes involved in genetic regulation including epigenetic, transcriptional, and post-transcriptional regulation. In this review, we discuss the fundamental functions of lncRNAs at different regulatory levels and their roles in metabolic balance. Typical examples are introduced to illustrate their diverse molecular mechanisms. The comprehensive investigation and identification of key lncRNAs will not only contribute to insights into diseases, such as breast cancer and type II diabetes, but also provide promising therapeutic targets for related diseases.

• Molecules and Cells
• /
• 제37권5호
• /
• pp.357-364
• /
• 2014

Medulloblastoma, the most common malignant brain tumor in children, is a disease whose mechanisms are now beginning to be uncovered by high-throughput studies of somatic mutations, mRNA expression patterns, and epigenetic profiles of patient tumors. One emerging theme from studies that sequenced the tumor genomes of large cohorts of medulloblastoma patients is frequent mutation of RNA binding proteins. Proteins which bind multiple RNA targets can act as master regulators of gene expression at the post-transcriptional level to co-ordinate cellular processes and alter the phenotype of the cell. Identification of the target genes of RNA binding proteins may highlight essential pathways of medulloblastomagenesis that cannot be detected by study of transcriptomics alone. Furthermore, a subset of RNA binding proteins are attractive drug targets. For example, compounds that are under development as anti-viral targets due to their ability to inhibit RNA helicases could also be tested in novel approaches to medulloblastoma therapy by targeting key RNA binding proteins. In this review, we discuss a number of RNA binding proteins, including Musashi1 (MSI1), DEAD (Asp-Glu-Ala-Asp) box helicase 3 X-linked (DDX3X), DDX31, and cell division cycle and apoptosis regulator 1 (CCAR1), which play potentially critical roles in the growth and/or maintenance of medulloblastoma.

• BMB Reports
• /
• 제52권2호
• /
• pp.127-132
• /
• 2019

Cells must fine-tune their gene expression programs for optimal cellular activities in their natural growth conditions. Transcriptional memory, a unique transcriptional response, plays a pivotal role in faster reactivation of genes upon environmental changes, and is facilitated if genes were previously in an active state. Hyper-activation of gene expression by transcriptional memory is critical for cellular differentiation, development, and adaptation. TREM (Transcriptional REpression Memory), a distinct type of transcriptional memory, promoting hyper-repression of unnecessary genes, upon environmental changes has been recently reported. These two transcriptional responses may optimize specific gene expression patterns, in rapidly changing environments. Emerging evidence suggests that they are also critical for immune responses. In addition to memory B and T cells, innate immune cells are transcriptionally hyperactivated by restimulation, with the same or different pathogens known as trained immunity. In this review, we briefly summarize recent progress in chromatin-based regulation of transcriptional memory, and its potential role in immune responses.

• 한국동물번식학회:학술대회논문집
• /
• 한국동물번식학회 2004년도 춘계학술발표대회
• /
• pp.189-189
• /
• 2004

Histone acetylation as epigenetic marker plays a critical role in gene expression through the interaction of nucleosomes with DNA, modulating the efficiency which RNA-polymerase can interact with promotors to initiate transcription. After fertilization, highly acetylated chromatin takes place and maintain during 1cell stages. The hyperacetylation may lead minor genome activation for survival and cleavage, and then may affect embryonic genome activation and development to balstocyst. (omitted)

• 한국발생생물학회지:발생과생식
• /
• 제15권3호
• /
• pp.187-195
• /
• 2011

X chromosome inactivation (XCI) is a process that enables mammalian females to ensure the dosage compensation for X-linked genes. Investigating the mechanism of XCI might provide deeper understandings of chromosomal silencing, epigenetic regulation of gene expressions, and even the course of evolution. Studies on mammalian XCI conducted with mice have revealed many fundamental findings on XCI. However, difference of murine and human XCI necessitates the further investigation in human XCI. Recent success in reprogramming of differentiated cells into pluripotent stem cells showed the reversibility of XCI in vitro, X chromosome reactivation (XCR), which provides another tool to study the change in X chromosome status. This review summarizes the current knowledge of XCI during early embryonic development and describes recent achievements in studies of XCI in reprogramming process.

• Interdisciplinary Bio Central
• /
• 제1권1호
• /
• pp.4.1-4.7
• /
• 2009

Introduction: Histone modifications and DNA methylation are the major factors in epigenetic gene regulation. Especially, revealing how histone modifications are related to DNA methylation is one of the challenging problems in this field. In this paper, we address this issue and propose several plausible mechanisms for precise controlling of DNA methylation status at CpG islands. Materials and Methods: To establish the regulatory relationships, we used 38 histone modification types including H2A.Z and CTCF, and DNA methylation status at CpG islands across chromosome 6, 20, and 22 of human CD4+ T cell. We utilized Bayesian network to construct regulatory network. Results and Discussion: We found several meaningful relationships supported by previous studies. In addition, our results show that histone modifications can be clustered into several groups with different regulatory properties. Based on those findings we predicted the status of methylation level at CpG islands with high accuracy, and suggested core-regulatory network to control DNA methylation status.