• Asian-Australasian Journal of Animal Sciences
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• 제30권11호
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• pp.1529-1539
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• 2017

Objective: The objective of this study was to compare the DNA methylation profile in the longissimus dorsi muscle between Small Tailed Han and Dorper${\times}$Small Tailed Han crossbred sheep which were known to exhibit significant difference in meat-production. Methods: Six samples (three in each group) were subjected to the methylated DNA immunoprecipitation sequencing (MeDIP-seq) and subsequent bioinformatics analyses to detect differentially methylated regions (DMRs) between the two groups. Results: 23.08 Gb clean data from six samples were generated and 808 DMRs were identified in gene body or their neighboring up/downstream regions. Compared with Small Tailed Han sheep, we observed a tendency toward a global loss of DNA methylation in these DMRs in the crossbred group. Gene ontology enrichment analysis found several gene sets which were hypomethylated in gene-body region, including nucleoside binding, motor activity, phospholipid binding and cell junction. Numerous genes were found to be differentially methylated between the two groups with several genes significantly differentially methylated, including transforming growth factor beta 3 (TGFB3), acyl-CoA synthetase long chain family member 1 (ACSL1), ryanodine receptor 1 (RYR1), acyl-CoA oxidase 2 (ACOX2), peroxisome proliferator activated receptor-gamma2 (PPARG2), netrin 1 (NTN1), ras and rab interactor 2 (RIN2), microtubule associated protein RP/EB family member 1 (MAPRE1), ADAM metallopeptidase with thrombospondin type 1 motif 2 (ADAMTS2), myomesin 1 (MYOM1), zinc finger, DHHC type containing 13 (ZDHHC13), and SH3 and PX domains 2B (SH3PXD2B). The real-time quantitative polymerase chain reaction validation showed that the 12 genes are differentially expressed between the two groups. Conclusion: In the current study, a tendency to a global loss of DNA methylation in these DMRs in the crossbred group was found. Twelve genes, TGFB3, ACSL1, RYR1, ACOX2, PPARG2, NTN1, RIN2, MAPRE1, ADAMTS2, MYOM1, ZDHHC13, and SH3PXD2B, were found to be differentially methylated between the two groups by gene ontology enrichment analysis. There are differences in the expression of 12 genes, of which ACSL1, RIN2, and ADAMTS2 have a negative correlation with methylation levels and the data suggest that DNA methylation levels in DMRs of the 3 genes may have an influence on the expression. These results will serve as a valuable resource for DNA methylation investigations on screening candidate genes which might be related to meat production in sheep.

• 생명과학회지
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• 제27권7호
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• pp.840-848
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• 2017

세포내 수송 기구는 세포의 작용과 생존에 필수적이다. 이러한 세포내 수송은 긴 미세소관을 따라서 운반체를 운반하는 미세소관 의존 분자 모터 단백질인 kinesin과 cytoplasmic dynein에 의하여 이루어진다. Kinesin은 ATP 의존적으로 미세소관의 plus-end방향으로 이동하는 모터 단백질로 세포내 소기관, 분비소포, RNA 복합체, 단백질 복합체들을 수송한다. Kinesins에 의한 다양한 운반체의 수송의 이상은 세포의 기능 이상과 연관된다. Kinesins에 의한 운반체 수송의 기본 단계는: 운반체 혹은 adaptor 단백질과의 결합, kinesin 기능 활성화와 미세소관을 따라서 이동, 그리고 올바른 위치에서 운반체와의 분리 단계로 나뉘어 진다. 최근의 연구결과들에서 kinesin 모터 기능 활성화, 운반체와의 결합, 운반체와의 해리 기전이 확인되고 있으며 세포내 운반체 수송은 kinesin과 운반체를 연결하는 adaptor 단백질에 의하여서도 조절된다. 단백질 인산화 효소, 탈 인산화 효소를 포함하는 kinesin 모터 활성 조절 단백질들은 kinesin의 인산화 혹은 탈 인산화를 통하여 직접적으로 세포내 수송을 조절하거나, c-Jun NH-terminal kinase-interacting proteins (JIPs)와 같은 adaptor 단백질들과 미세소관의 간접적 수식을 통하여 세포내 수송을 조절하기도 한다. 이러한 연구결과들은 세포의 기능과 형태 유지에 관여하는 kinesin에 의한 다양한 세포내 수송 조절 기전을 이해하는데 기초적인 토대가 된다. 또한 각각의 kinesin에 대한 조절 기전을 밝히는 것은 세포생물학과 신경생리학을 이해하는데 중요하므로 본 종설에서는 kinesin에 의한 세포내 수송을 조절하는 단백질과 kinesin과 수송체와의 결합이 어떻게 조절되는지를 고찰하고자 한다.

• International Journal of Oral Biology
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• 제31권2호
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• pp.53-65
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• 2006

Calcium concentration in the bone resorption lacunae is high and is in the mM concentration range. Both osteoblast and osteoclast have calcium sensing receptor in the cell surface, suggesting the regulatory role of high extracellular calcium in bone metabolism. In vitro, high extracellular calcium stimulated osteoclastogenesis in coculture of mouse osteoblasts and bone marrow cells. Therefore we examined the genes that were commonly regulated by both high extracellular calcium and $1,25(OH)_2vitaminD_3(VD3)$ by using mouse oligo 11 K gene chip. In the presence of 10 mM $[Ca^{2+}]e$ or 10 nM VD3, mouse calvarial osteoblasts and bone marrow cells were co-cultured for 4 days when tartrate resistant acid phosphatase-positive multinucleated cells start to appear. Of 11,000 genes examined, the genes commonly regulated both by high extracellular calcium and by VD3 were as follows; 1) the expression of genes which were osteoclast differentiation markers or were associated with osteoclastogenesis were up-regulated both by high extracellular calcium and by VD3; trap, mmp9, car2, ctsk, ckb, atp6b2, tm7sf4, rab7, 2) several chemokine and chemokine receptor genes such as sdf1, scya2, scyb5, scya6, scya8, scya9, and ccr1 were up-regulated both by high extracellular calcium and by VD3, 3) the genes such as mmp1b, mmp3 and c3 which possibly stimulate bone resorption by osteoclast, were commonly up-regulated, 4) the gene such as c1q and msr2 which were related with macrophage function, were commonly down-regulated, 5) the genes which possibly stimulate osteoblast differentiation and/or mineralization of extracellular matrix, were commonly down-regulated; slc8a1, admr, plod2, lox, fosb, 6) the genes which possibly suppress osteoblast differentiation and/or mineralization of extracellular matrix, were commonly up-regulated; s100a4, npr3, mme, 7) the genes such as calponin 1 and tgfbi which possibly suppress osteoblast differentiation and/or mineralization of extracellular matrix, were up-regulated by high extracellular calcium but were down-regulated by VD3. These results suggest that in coculture condition, both high extracellular calcium and VD3 commonly induce osteoclastogenesis but suppress osteoblast differentiation/mineralization by regulating the expression of related genes.

• Journal of Genetic Medicine
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• 제14권1호
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• pp.8-17
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• 2017

Purpose: Pulse wave velocity (PWV) is an indicator of arterial stiffness, and is considered a marker of vascular damage. However, a genome-wide association study analyzing single nucleotide polymorphisms (SNPs) associated with brachial-ankle PWV (baPWV) has not been conducted in healthy populations. We performed this study to identify SNPs associated with baPWV in healthy populations in Korea. Materials and Methods: Genomic SNPs data for 2,407 individuals from three sites were analyzed as part of the Korean Genomic Epidemiologic Study. Without replication samples, we performed multivariable analysis as a post hoc analysis to verify the findings in site adjusted analysis. Healthy subjects aged between 40 and 70 years without self-reported history or diagnosis of hypertension, diabetes, hyperlipidemia, heart disease, cerebrovascular disease and cancer were included. We excluded subjects with a creatinine level >1.4 mg/dL (men) and 1.2 mg/dL (women). Results: In the site-adjusted association analysis, significant associations (P<$5{\times}10^{-8}$) with baPWV were detected for only 5 SNPs with low minor allele frequency. In multivariable analysis adjusted by age, sex, height, body mass index, mean arterial pressure, site, smoking, alcohol, and exercise, 11 SNPs were found to be associated (P<$5{\times}10^{-8}$) with baPWV. The 5 SNPs (P<$5{\times}10^{-8}$) linked to three genes (OPCML, PRR35 and RAB40C) were common between site-adjusted analysis and multivariable analysis. However, meta-analysis of the result from three sites for the 11 SNPs showed no significant associations. Conclusion: Using the recent standard for genome-wide association study, we did not find any evidence of significant association signals with baPWV.