Epigenetics: general characteristics and implications for oral health

Seo, Ji-Yun,Park, Yoon-Jung,Yi, Young-Ah,Hwang, Ji-Yun,Lee, In-Bog,Cho, Byeong-Hoon,Son, Ho-Hyun,Seo, Deog-Gyu The Korean Academy of Conservative Dentistry 2015 Restorative Dentistry & Endodontics Vol.40 No.1

Genetic information such as DNA sequences has been limited to fully explain mechanisms of gene regulation and disease process. Epigenetic mechanisms, which include DNA methylation, histone modification and non-coding RNAs, can regulate gene expression and affect progression of disease. Although studies focused on epigenetics are being actively investigated in the field of medicine and biology, epigenetics in dental research is at the early stages. However, studies on epigenetics in dentistry deserve attention because epigenetic mechanisms play important roles in gene expression during tooth development and may affect oral diseases. In addition, understanding of epigenetic alteration is important for developing new therapeutic methods. This review article aims to outline the general features of epigenetic mechanisms and describe its future implications in the field of dentistry.

Epigenetics: general characteristics and implications for oral health

서지윤,박윤정,이영아,황지윤,이인복,조병훈,손호현,서덕규 대한치과보존학회 2015 Restorative Dentistry & Endodontics Vol.40 No.1

Genetic information such as DNA sequences has been limited to fully explain mechanisms of gene regulation and disease process. Epigenetic mechanisms, which include DNA methylation, histone modification and non-coding RNAs, can regulate gene expression and affect progression of disease. Although studies focused on epigenetics are being actively investigated in the field of medicine and biology, epigenetics in dental research is at the early stages. However, studies on epigenetics in dentistry deserve attention because epigenetic mechanisms play important roles in gene expression during tooth development and may affect oral diseases. In addition, understanding of epigenetic alteration is important for developing new therapeutic methods. This review article aims to outline the general features of epigenetic mechanisms and describe its future implications in the field of dentistry.

Aberrant Epigenetic Alteration in Eca9706 Cells Modulated by Nanoliposomal Quercetin Combined with Butyrate Mediated via Epigenetic-NF-κB Signaling

Zheng, Nai-Gang,Wang, Jun-Ling,Yang, Sheng-Li,Wu, Jing-Lan Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.11

Since the epigenetic alteration in tumor cells can be reversed by the dietary polyphenol quercetin (Q) or butyrate (B) with chemopreventive activity, suggesting that Q or B can be used for chemopreventive as well as therapeutic agent against tumors. In this study the polyphenol flavonoid quercetin (Q) or sodium butyrate (B) suppressed human esophageal 9706 cancer cell growth in dose dependent manner, and Q combined with B (Q+B) could further inhibit Eca9706 cell proliferation than that induced by Q or B alone, compared with untreated control group (C) in MTT assay. The reverse expressions of global DNMT1, $NF-{\kappa}Bp65$, HDAC1 and Cyclin D1 were down-regulated, while expressions of caspase-3 and $p16INK4{\alpha}$ were up-regulated, compared with the C group in immunoblotting; the down-regulated HDAC1-IR (-immunoreactivity) with nuclear translocation, and up-regulated E-cadherin-IR demonstrated in immunocytochemistry treated by Q or B, and Q+B also displayed further negatively and positively modulated effects compared with C group. The order of methylation specific (MS) PCR of $p16INK4{\alpha}$: C>B/Q>Q+B group, while the order of E-cadherin expression level was contrary, Q+B>Q/B>C group. Thus, Q/B, especially Q+B display reverse effect targeting both altered DNA methylation and histone acetylation, acting as histone deacetylase inhibitor mediated via epigenetic-$NF-{\kappa}B$ cascade signaling.

후생유전학 (Epigenetics)과 DNA methylation의 이해

오정환,권용대,윤병욱,최병준,Oh, Jung-Hwan,Kwon, Young-Dae,Yoon, Byung-Wook,Choi, Byung-Jun 대한악안면성형재건외과학회 2008 Maxillofacial Plastic Reconstructive Surgery Vol.30 No.3

DNA 메틸화는 histone modification과 함께 DNA의 염기서열이 유지되면서 유전기능이 변화되고 자손까지 전달 될 수 있는 후생 유전의 중요한 한 부분이다. DNA 메틸화는 크로마틴의 구조를 변경시키는 과정을 통하여 유전자와 repetitive sequence의 표현을 억제시킬 수 있다. DNA 메틸화는 X-불활성화, 유전체 각인, 유전자 발현조절, 암 생성 등에 중요한 역할을 하는 것으로 밝혀졌고, DNA 메틸화 표지자 (DNA methylation marker)들은 종양의 진단과 치료에 대한 반응을 예측하는 지표로 활용되고 있다. 지금까지 많은 연구 성과에도 불구하고 DNA메틸화, 메틸화에 의한 gene silencing, DNA 메틸화의 표적부위 등에 대한 명확한 기전이 아직도 밝혀지지 않고 있어 향후 더 많은 기초적 연구가 필요할 것이다. 최근에는 후생 유전적 변화는 가역적이기 때문에 종양억제유전자를 억압하는 후생 유전적 변화를 제거한다면 그 종양억제유전자를 다시 활성화시킬 수 있다는 개념의 후생유전 치료법 연구로 DNA 메틸화 억제제와 histone deacetyaltion에 관여하는 HDAC의 억제제들이 항암제로서 개발되어 사용되고 있는데 향후 더 많은 약제 개발과 임상적 연구가 진행되어야 할 것이다. Epigenetic is usually referring to heritable traits that do not involve changes to the underlying DNA sequence. DNA methylation is known to serve as cellular memory. and is one of the most important mechanism of epigenetic. DNA methylation is a covalent modification in which the target molecules for methylation in mammalian DNA are cytosine bases in CpG dinucleotides. The 5' position of cytosine is methylated in a reaction catalyzed by DNA methyltransferases; DNMTl, DNMT3a, and DNMT3b. There are two different regions in the context of DNA methylation: CpG poor regions and CpG islands. The intergenic and the intronic region is considered to be CpG poor, and CpG islands are discrete CpG-rich regions which are often found in promoter regions. Normally, CpG poor regions are usually methylated whereas CpG islands are generally hypomethylated. DNA methylation is involved in various biological processes such as tissue-specific gene expression, genomic imprinting, and X chromosome inactivation. In general. cancer cells are characterized by global genomic hypomethylation and focal hypermethylation of CpG islands, which are generally unmethylated in normal cells. Gene silencing by CpG hypermethylation at the promotors of tumor suppressor genes is probably the most common mechanism of tumor suppressor inactivation in cancer.

Cloning of the Setd1b gene of Mus musculus, a novel histone methyl transferase target in the epigenetic therapy of cancers

Morishita, Masayo,Cho, Minju,Ryu, Juhee,Mevius, Damiaan E.H.F.,Di Luccio, Eric 경북대학교 농업과학기술연구소 2010 慶北大農學誌 Vol.28 No.-

The epigenetic therapy of cancers is emerging as an effective and valuable approach to both chemotherapy and the chemoprevention of cancer. The utilization of epigenetic targets that include histone methyltransferase (HMTase), Histone deacetylatase, and DNA methyltransferase, are emerging as key therapeutic targets. SET containing proteins such as the HMTase Setd1b has been found significantly amplified in cancerous cells. In order to shed some light on the histone methyl transferase family, we cloned the Setd1b gene from Mus musculus and build a collection of vectors for recombinant protein expression in E.coli that will pave the way for further structural biology studies. We prospect the role of the Setd1b pathway in cancer therapy and detail its unique value for designing novel anti-cancer epigenetic-drugs.

Polymorphisms in Epigenetic and Meat Quality Related Genes in Fourteen Cattle Breeds and Association with Beef Quality and Carcass Traits

Liu, Xuan,Usman, Tahir,Wang, Yachun,Wang, Zezhao,Xu, Xianzhou,Wu, Meng,Zhang, Yi,Zhang, Xu,Li, Qiang,Liu, Lin,Shi, Wanhai,Qin, Chunhua,Geng, Fanjun,Wang, Congyong,Tan, Rui,Huang, Xixia,Liu, Airong,Wu, Asian Australasian Association of Animal Productio 2015 Animal Bioscience Vol.28 No.4

Improvement for carcass traits related to beef quality is the key concern in beef production. Recent reports found that epigenetics mediates the interaction of individuals with environment and nutrition. The present study was designed to analyze the genetic effect of single nucleotide polymorphisms (SNPs) in seven epigenetic-related genes (DNMT1, DNMT3a, DNMT3b, DNMT3L, Ago1, Ago2, and HDAC5) and two meat quality candidate genes (CAPN1 and PRKAG3) on fourteen carcass traits related to beef quality in a Snow Dragon beef population, and also to identify SNPs in a total of fourteen cattle populations. Sixteen SNPs were identified and genotyped in 383 individuals sampled from the 14 cattle breeds, which included 147 samples from the Snow Dragon beef population. Data analysis showed significant association of 8 SNPs within 4 genes related to carcass and/or meat quality traits in the beef populations. SNP1 (13154420A>G) in exon 17 of DNMT1 was significantly associated with rib-eye width and lean meat color score (p<0.05). A novel SNP (SNP4, 76198537A>G) of DNMT3a was significantly associated with six beef quality traits. Those individuals with the wild-type genotype AA of DNMT3a showed an increase in carcass weight, chilled carcass weight, flank thicknesses, chuck short rib thickness, chuck short rib score and in chuck flap weight in contrast to the GG genotype. Five out of six SNPs in DNMT3b gene were significantly associated with three beef quality traits. SNP15 (45219258C>T) in CAPN1 was significantly associated with chuck short rib thickness and lean meat color score (p<0.05). The significant effect of SNP15 on lean meat color score individually and in combination with each of other 14 SNPs qualify this SNP to be used as potential marker for improving the trait. In addition, the frequencies of most wild-type alleles were higher than those of the mutant alleles in the native and foreign cattle breeds. Seven SNPs were identified in the epigenetic-related genes. The SNP15 in CAPN1 could be used as a powerful genetic marker in selection programs for beef quality improvement in the Snow Dragon Beef population.

Polymorphisms in Epigenetic and Meat Quality Related Genes in Fourteen Cattle Breeds and Association with Beef Quality and Carcass Traits

Xuan Liu,Tahir Usman,Yachun Wang,Zezhao Wang,Xianzhou Xu,Meng Wu,Yi Zhang,Xu Zhang,Qiang Li,Lin Liu,Wanhai Shi,Chunhua Qin,Fanjun Geng,Congyong Wang,Rui Tan,Xixia Huang,Airong Liu,Hongjun Wu,Shixin Ta 아세아·태평양축산학회 2015 Animal Bioscience Vol.28 No.4

Improvement for carcass traits related to beef quality is the key concern in beef production. Recent reports found that epigenetics mediates the interaction of individuals with environment and nutrition. The present study was designed to analyze the genetic effect of single nucleotide polymorphisms (SNPs) in seven epigenetic-related genes (DNMT1, DNMT3a, DNMT3b, DNMT3L, Ago1, Ago2, and HDAC5) and two meat quality candidate genes (CAPN1 and PRKAG3) on fourteen carcass traits related to beef quality in a Snow Dragon beef population, and also to identify SNPs in a total of fourteen cattle populations. Sixteen SNPs were identified and genotyped in 383 individuals sampled from the 14 cattle breeds, which included 147 samples from the Snow Dragon beef population. Data analysis showed significant association of 8 SNPs within 4 genes related to carcass and/or meat quality traits in the beef populations. SNP1 (13154420A>G) in exon 17 of DNMT1 was significantly associated with rib-eye width and lean meat color score (p<0.05). A novel SNP (SNP4, 76198537A>G) of DNMT3a was significantly associated with six beef quality traits. Those individuals with the wild-type genotype AA of DNMT3a showed an increase in carcass weight, chilled carcass weight, flank thicknesses, chuck short rib thickness, chuck short rib score and in chuck flap weight in contrast to the GG genotype. Five out of six SNPs in DNMT3b gene were significantly associated with three beef quality traits. SNP15 (45219258C>T) in CAPN1 was significantly associated with chuck short rib thickness and lean meat color score (p<0.05). The significant effect of SNP15 on lean meat color score individually and in combination with each of other 14 SNPs qualify this SNP to be used as potential marker for improving the trait. In addition, the frequencies of most wild-type alleles were higher than those of the mutant alleles in the native and foreign cattle breeds. Seven SNPs were identified in the epigenetic-related genes. The SNP15 in CAPN1 could be used as a powerful genetic marker in selection programs for beef quality improvement in the Snow Dragon Beef population.

GENETIC AND EPIGENETIC FACTORS AFFECTING CHICKEN TELOMERE AMOUNT

Vinod K Subramani,Soo Hee Lee,Na Eun Choi,Sea Hwan Sohn 한국가금학회 2009 한국가금학회 정기총회 및 학술발표회 Vol.26 No.-

Telomeres are specialized eukaryotic chromosome end structures, comprised of tandem repeats of TTAGGG sequence and associated proteins. Aves in general, are interesting models for molecular studies on aging and cellular senescence as they have remarkably slow aging rates and longer life spans for their size. In this study, we look at the genetic and epigenetic/environmental factors that influence telomere quantity in chickens. We quantified the relative amount of telomeric DNA in isolated interphase peripheral blood lymphocytes by the Quantitative Fluorescent In Situ Hybridization technique using telomere specific DNA probes. This study was carried out to investigate the role of predominant genetic and epigenetic or environmental factors that may influence the poultry industry at the telomere level which in turn affects the biological age of the animal.

Epigenetic Regulation of Cancer-Associated Genes in Ovarian Cancer

Kwon, Mi Jeong,Shin, Young Kee Molecular Diversity Preservation International (MD 2011 INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES Vol.12 No.2

<P>The involvement of epigenetic aberrations in the development and progression of tumors is now well established. However, most studies have focused on the epigenetic inactivation of tumor suppressor genes during tumorigenesis and little is known about the epigenetic activation of cancer-associated genes, except for the DNA hypomethylation of some genes. Recently, we reported that the overexpression of cancer-promoting genes in ovarian cancer is associated with the loss of repressive histone modifications. This discovery suggested that epigenetic derepression may contribute to ovarian tumorigenesis by constituting a possible mechanism for the overexpression of oncogenes or cancer-promoting genes in tumors. The emerging importance of epigenetic aberrations in tumor initiation and in the regulation of cancer-initiating cells, suggests that epigenetically regulated genes may be promising therapeutic targets and biomarkers. Given that the current challenges in ovarian cancer include the identification of biomarkers for early cancer detection and the discovery of novel therapeutic targets for patients with recurrent malignancies undergoing chemotherapy, understanding the epigenetic changes that occur in ovarian cancer is crucial. This review looks at epigenetic mechanisms involved in the regulation of cancer-associated genes, including the contribution of epigenetic derepression to the activation of cancer-associated genes in ovarian cancer. In addition, possible epigenetic therapies targeting epigenetically dysregulated genes are discussed. A better understanding of the epigenetic changes in ovarian cancer will contribute to the improvement of patient outcomes.</P>

Genetic and epigenetic variation in mass selection populations of Pacific oyster Crassostrea gigas

Qun Jiang,Qi Li,Hong Yu,Lingfeng Kong 한국유전학회 2013 Genes & Genomics Vol.35 No.5

Selective breeding often produces an improvementin phenotype. Much of the phenotypic change withina species is a consequence of genetic variation. However,there is growing evidence for phenotypic change even inthe absence of DNA sequence polymorphisms, termedepigenetic variation. This study’s goal was to investigatethe genetic and epigenetic variation in the mass selectionpopulations of the Pacific oyster (Crassostrea gigas),determine if any correlation exists between the genetic andepigenetic variations. This can serve as a first step ininvestigating the potential role epigenetic variations havein selective breeding. Amplified fragment length polymorphismanalysis and methylation-sensitive amplifiedpolymorphism methodology were used to monitor geneticand epigenetic variation in two populations (the base stockand the third selected generation) from a mass selectionline in the Pacific oyster. The correlation between geneticand epigenetic variation was evaluated by Co-InertiaAnalysis. The genetic difference was mainly found in thegene frequency shift revealed by the FST value (0.0151,P\0.01) and no significant reduction in genetic diversitywas detected. The percentage of methylation in C. gigaswas 26.4 %. No significant difference was observed on theaverage state of methylation, but a few bands showed differentfrequencies between the two populations. Co-InertiaAnalysis revealed a significant association between thegenetic and epigenetic profiles (P\0.01). Selective breeding often produces an improvement in phenotype. Much of the phenotypic change within a species is a consequence of genetic variation. However, there is growing evidence for phenotypic change even in the absence of DNA sequence polymorphisms, termed epigenetic variation. This study’s goal was to investigate the genetic and epigenetic variation in the mass selection populations of the Pacific oyster (Crassostrea gigas), determine if any correlation exists between the genetic and epigenetic variations. This can serve as a first step in investigating the potential role epigenetic variations have in selective breeding. Amplified fragment length polymorphism analysis and methylation-sensitive amplified polymorphism methodology were used to monitor genetic and epigenetic variation in two populations (the base stock and the third selected generation) from a mass selection line in the Pacific oyster. The correlation between genetic and epigenetic variation was evaluated by Co-Inertia Analysis. The genetic difference was mainly found in the gene frequency shift revealed by the FST value (0.0151, P\0.01) and no significant reduction in genetic diversity was detected. The percentage of methylation in C. gigas was 26.4 %. No significant difference was observed on the average state of methylation, but a few bands showed different frequencies between the two populations. Co-Inertia Analysis revealed a significant association between the genetic and epigenetic profiles (P\0.01).