• Asian-Australasian Journal of Animal Sciences
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• v.30 no.11
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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.

• Journal of Life Science
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• v.27 no.7
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• pp.840-848
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• 2017

Proper intracellular transport is essential for normal cell function. Intracellular transport is mediated by microtubule-dependent molecular motor proteins, as well as kinesin and cytoplasmic dynein, which move their cargo along long, microtubule tracks in cells. Kinesins are ATP-dependent plus-end-directed motor proteins in the intracellular transport of organelles, vesicles, RNA complexes, and protein complexes. The mislocalization of these different types of cargo has been linked to cell dysfunction and degeneration. The cargo transport of kinesins can be described by the following steps: binding to the appropriate cargo and/or adaptor proteins, activation of the kinesin's motility and movement along the microtubule, and the release of the cargo at the correct destination. Recently, several studies have revealed the mechanisms for the regulation of kinesin motor activity, including cargo loading and unloading. Intracellular cargo transport is also modulated by adaptor proteins, which link the kinesins to their cargo. The regulatory proteins, which include protein kinases and phosphatases, regulate kinesin motor activity directly through the phosphorylation or dephosphorylation of kinesins and indirectly through the modification of adaptor proteins, such as c-Jun NH-terminal kinase-interacting proteins, or of the microtubule network. These findings lay the groundwork for understanding how kinesins are differentially engaged in intracellular cargo transport. In addition, understanding the regulatory mechanisms of each kinesin is an area of key interest within cell biology and neurophysiology. In this study, we reviewed kinesins' regulation proteins and discuss how their regulation affects cargo recognition and transport.

• International Journal of Oral Biology
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• v.31 no.2
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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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• v.14 no.1
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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.