• BMB Reports
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• 제49권12호
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• pp.671-680
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• 2016

Accumulating evidence indicates many brain functions are mediated by epigenetic regulation of neural genes, and their dysregulations result in neuronal disorders. Experiences such as learning and recall, as well as physical exercise, induce neuronal activation through epigenetic modifications and by changing the noncoding RNA profiles. Animal models, brain samples from patients, and the development of diverse analytical methods have broadened our understanding of epigenetic regulation in the brain. Diverse and specific epigenetic changes are suggested to correlate with neuronal development, learning and memory, aging and age-related neuronal diseases. Although the results show some discrepancies, a careful comparison of the data (including methods, regions and conditions examined) would clarify the problems confronted in understanding epigenetic regulation in the brain.

• BMB Reports
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• 제43권10호
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• pp.649-655
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• 2010

Alzheimer's disease (AD) is the most common age-dependent neurodegenerative disorder and shows progressive memory loss and cognitive decline. Intraneuronal filaments composed of aggregated hyperphosphorylated tau protein, called neurofibrillary tangles, along with extracellular accumulations of amyloid $\beta$ protein (A$\beta$), called senile plaques, are known to be the neuropathological hallmarks of AD. In light of recent studies, epigenetic modification has emerged as one of the pathogenic mechanisms of AD. Epigenetic changes encompass an array of molecular modifications to both DNA and chromatin, including transcription factors and cofactors. In this review, we summarize how DNA methylation and changes to DNA chromatin packaging by post-translational histone modification are involved in AD. In addition, we describe the role of SIRTs, histone deacetylases, and the effect of SIRT-modulating drugs on AD. Lastly, we discuss how amyloid precursor protein (APP) intracellular domain (AICD) regulates neuronal transcription. Our understanding of the epigenomes and transcriptomes of AD may warrant future identification of novel biological markers and beneficial therapeutic targets for AD.

• IMMUNE NETWORK
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• 제23권1호
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• pp.5.1-5.28
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• 2023

Th cell lineage determination and functional specialization are tightly linked to the activation of lineage-determining transcription factors (TFs) that bind cis-regulatory elements. These lineage-determining TFs act in concert with multiple layers of transcriptional regulators to alter the epigenetic landscape, including DNA methylation, histone modification and threedimensional chromosome architecture, in order to facilitate the specific Th gene expression programs that allow for phenotypic diversification. Accumulating evidence indicates that Th cell differentiation is not as rigid as classically held; rather, extensive phenotypic plasticity is an inherent feature of T cell lineages. Recent studies have begun to uncover the epigenetic programs that mechanistically govern T cell subset specification and immunological memory. Advances in next generation sequencing technologies have allowed global transcriptomic and epigenomic interrogation of CD4+ Th cells that extends previous findings focusing on individual loci. In this review, we provide an overview of recent genome-wide insights into the transcriptional and epigenetic regulation of CD4+ T cell-mediated adaptive immunity and discuss the implications for disease as well as immunotherapies.

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

• BMB Reports
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• 제55권7호
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• pp.342-347
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• 2022

Defense priming allows plants to enhance their immune responses to subsequent pathogen challenges. Recent reports suggested that acquired resistances in parental generation can be inherited into descendants. Although epigenetic mechanisms are plausible tools enabling the transmission of information or phenotypic traits induced by environmental cues across generations, the mechanism for the transgenerational inheritance of defense priming in plants has yet to be elucidated. With the initial aim to elucidate an epigenetic mechanism for the defense priming in plants, we reassessed the transgenerational inheritance of plant defense, however, could not observe any evidence supporting it. By using the same dipping method with previous reports, Arabidopsis was exposed repeatedly to Pseudomonas syringae pv tomato DC3000 (Pst DC3000) during vegetative or reproductive stages. Irrespective of the developmental stages of parental plants that received pathogen infection, the descendants did not exhibit primed resistance phenotypes, defense marker gene (PR1) expression, or elevated histone acetylation within PR1 chromatin. In assays using the pressure-infiltration method for infection, we obtained the same results as above. Thus, our results suggest that the previous observations on the transgenerational inheritance of defense priming in plants should be more extensively and carefully reassessed.

• 생명과학회지
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• 제17권3호통권83호
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• pp.444-453
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• 2007

유핵세포의 게놈(genome)은 단백-DNA복합체인 염색질(chromatin)의 형태로 존재하는데, 생명현상을 유지하기 위해서는 생명체 또는 세포가 처한 상황에 맞게 염색질의 구조를 변화시키는 역동적인 조절기전이 필요하다. 염색질을 구성하는 기본단위는 히스톤 8량체 (histone octamer)를 포함하는 뉴클레오좀(nucleosome)이다. 히스톤 단백에는 여러 종류의 공유결합성 수식이 일어나는데, 그 중 하나가 라이신 잔기(lysine residue)에 일어나는 메틸화이다. 최근 수년간의 연구로 여러 개의 히스톤 라이신 메틸화효소(histone lysine methyltransferase, HKMT), 이에 결합하는 염색질단백 및 메틸화와 관련된 후생유전학적 현상이 밝혀졌으며, 특히 정밀한 연구방법을 동원한 다방면의 실험을 통하여 비록 자세한 기전과 전체적인 윤곽의 규명은 미흡하더라도 라이신 메틸화가 후생유전학적 변화를 초래하는 일부 과정이 규명 되었다. 또한 여러 종류의 라이신 탈메틸화효소가 최근에 발견됨에 따라, 아세틸화, 인산화등 다른 공유결합성 수식보다는 상대 적으로 안정되더라도, 히스톤 메 틸화로 유발되는 후생유전학적 변화가 불가역성이 아님을 알게 되었다.

• Molecules and Cells
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• 제42권12호
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• pp.828-835
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• 2019

PIWI Argonaute proteins and Piwi-interacting RNAs (piRNAs) are expressed in all animal species and play a critical role in cellular defense by inhibiting the activation of transposable elements in the germline. Recently, new evidence suggests that PIWI proteins and piRNAs also play important roles in various somatic tissues, including neurons. This review summarizes the neuronal functions of the PIWI-piRNA pathway in multiple animal species, including their involvement in axon regeneration, behavior, memory formation, and transgenerational epigenetic inheritance of adaptive memory. This review also discusses the consequences of dysregulation of neuronal PIWI-piRNA pathways in certain neurological disorders, including neurodevelopmental and neurodegenerative diseases. A full understanding of neuronal PIWI-piRNA pathways will ultimately provide novel insights into small RNA biology and could potentially provide precise targets for therapeutic applications.

• 한국작물학회:학술대회논문집
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• 한국작물학회 2017년도 9th Asian Crop Science Association conference
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• pp.152-152
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• 2017

Plants exposed to environmental stress for long durations often can adapt to stress conditions with improved tolerance. Moreover this acquired tolerance to stress can be retained even after reverting to destressed growth conditions, which is known to stress memory. In these adaptation and stress memory processes, epigenetic regulation, such as DNA methylation and histone modifications play a key role. Here, we showed that regenerated rice plants from embryogenic callus exposed to gradually increasing NaCl concentrations (up to 120 mM NaCl) acquired salt tolerance and their enhanced tolerance are inherited to subsequent generations. The rice plants (R0) regenerated from rice callus under saline conditions were transplanted into normal paddy field and R1 seeds were harvested. These R1 seeds displayed higher germination rate on MS medium containing 100mM NaCl than wild-type. The callus derived from R1 seeds showed better growth than control callus on high salinity medium. And the salt-adapted R1 plants exhibited higher chlorophyll contents and also higher $K^+/Na^+$ ratio than wild-type rice under saline conditions. The results indicated that rice plants successfully adapted to saline growth conditions during regeneration on high salt medium and moreover this acquired tolerance to salt stress was inherited subsequent generation.

• Molecules and Cells
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• 제26권6호
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• pp.611-615
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• 2008

DNA methylation is an epigenetic mechanism for gene silencing. In Arabidopsis, MET1 is the primary DNA methyltransferase that maintains CG DNA methylation. Plants having an overall reduction of MET1 activity, caused by a met1 mutation or a constitutively expressed MET1 antisense gene, display genome hypomethylation, inappropriate gene and transposon transcription, and developmental abnormalities. However, the effect of a transient reduction in MET1 activity caused by inhibiting MET1 expression in a restricted set of cells is not known. For this reason, we generated transgenic plants with a MET1 antisense gene fused to the DEMETER (DME) promoter (DME:MET1 a/s). Here we show that DME is expressed in leaf primordia, lateral root primoridia, in the region distal to the primary root apical meristem, which are regions that include proliferating cells. Endogenous MET1 expression was normal in organs where the DME:MET1 a/s was not expressed. Although DME promoter is active only in a small set of cells, these plants displayed global developmental abnormalities. Moreover, centromeric repeats were hypomethylated. The developmental defects were accumulated by the generations. Thus, not maintaining CG methylation in a small population of proliferating cells flanking the meristems causes global developmental and epigenetic abnormalities that cannot be rescued by restoring MET1 activity. These results suggest that during plant development there is little or no short-term molecular memory for reestablishing certain patterns of CG methylation that are maintained by MET1. Thus, continuous MET1 activity in dividing cells is essential for proper patterns of CG DNA methylation and development.

• Journal of Periodontal and Implant Science
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• 제52권6호
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• pp.437-454
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• 2022

Embryonic stem cells have been a popular research topic in regenerative medicine owing to their pluripotency and applicability. However, due to the difficulty in harvesting them and their low yield efficiency, advanced cell reprogramming technology has been introduced as an alternative. Dental stem cells have entered the spotlight due to their regenerative potential and their ability to be obtained from biological waste generated after dental treatment. Cell reprogramming, a process of reverting mature somatic cells into stem cells, and transdifferentiation, a direct conversion between different cell types without induction of a pluripotent state, have helped overcome the shortcomings of stem cells and raised interest in their regenerative potential. Furthermore, the potential of these cells to return to their original cell types due to their epigenetic memory has reinforced the need to control the epigenetic background for successful management of cellular differentiation. Herein, we discuss all available sources of dental stem cells, the procedures used to obtain these cells, and their ability to differentiate into the desired cells. We also introduce the concepts of cell reprogramming and transdifferentiation in terms of genetics and epigenetics, including DNA methylation, histone modification, and non-coding RNA. Finally, we discuss a novel therapeutic avenue for using dental-derived cells as stem cells, and explain cell reprogramming and transdifferentiation, which are used in regenerative medicine and tissue engineering.