人类CD4~+T细胞中核小体定位与DNA甲基化的分布特征研究
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摘要
目的研究人类CD4~+T细胞中核小体定位与DNA甲基化位点的分布特征,探讨二者的相关性以及在基因表达过程中的作用机制。方法通过生物信息学匹配算法及分析方法,采用Perl语言和R语言进行编程,使用SAM进行差异表达基因筛选,通过David软件进行功能注释,研究人类CD4~+T细胞中核小体定位和甲基化位点的分布特征以及二者在基因表达中的作用。结果研究发现人类基因组7个分区中,核小体的甲基化水平在激活状态时呈下降趋势,在甲基化核小体定位的甲基化水平发生了明显的改变,与核小体定位模式密切相关。结论核小体定位和甲基化在基因组定位上具有协同关系,在基因表达调控中发挥着重要作用。
Objective To study the distribution characteristics of nucleosome positioning and DNA methylation in human CD4~+T cells,and to explore the correlation between them and the mechanism of their role obtained in gene expression. Methods Differentially expressed genes were obtained by SAM,and the function annotation was studied by David software,the distribution characteristics of nucleosome positioning and methylation sites and the role of both in gene expression were studied by bioinformatics matching algorithm and analysis method,programming was performed by Perl and R. Results Human genome 7 partition,consistently shown nucleosome level of methylation in the activated state were on the decline. The functional annotations of related genes showed similarities and differences,which were also closely related to the nucleosome localization model. Conclusion Nucleosome positioning and DNA methylation are synergistic in genomic localization and play an important role in regulating gene expression.
Objective To study the distribution characteristics of nucleosome positioning and DNA methylation in human CD4~+T cells,and to explore the correlation between them and the mechanism of their role obtained in gene expression. Methods Differentially expressed genes were obtained by SAM,and the function annotation was studied by David software,the distribution characteristics of nucleosome positioning and methylation sites and the role of both in gene expression were studied by bioinformatics matching algorithm and analysis method,programming was performed by Perl and R. Results Human genome 7 partition,consistently shown nucleosome level of methylation in the activated state were on the decline. The functional annotations of related genes showed similarities and differences,which were also closely related to the nucleosome localization model. Conclusion Nucleosome positioning and DNA methylation are synergistic in genomic localization and play an important role in regulating gene expression.
引文
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[8]Han H,Cortez CC,Yang X,et al. DNA methylation directly silences genes with non-CpG island promoters and establishes a nucleosome occupied promoter[J]. Hum Mol Genet,2011,20(22):4299-4310.
[9]Martino D,Maksimovic J,Joo JH,et al. Genome-scale profiling reveals a subset of genes regulated by DNA methylation that program somatic T-cell phenotypes in humans[J]. Genes Immun,2012,13(5):388-398.
[10]Chen K,Xi Y,Pan X,et al. DANPOS:Dynamic analysis of nucleosome position and occupancy by sequencing[J]. Genome Res,2013,23(2):341-351.
[11]Vladimir N,Babenko,Irina V. Chadaeva and Yuriy L. Orlov,Genomic landscape of CpG rich elements in human[J]. BMC Evol Biol,2017,17(1):19.
[2]Gonzaga-Jauregui C,Lupski JR,Gibbs RA,et al. Human genome sequencing in health and disease[J]. Annu Rev Med,2012,63:35-61.
[3]He YH,Yu Y,Zhang Y,et al. Genome-wide bovine H3K27me3modifications and the regulatory effects on genes expressions in peripheral blood lymphocytes[J]. PLo S One,2012,7(6):e39094.
[4]Schones DE,Cui K,Cuddapah S,et al. Dynamic Regulation of Nucleosome Positioning in the Human Genome[J]. Cell,2008,132(5):887-898.
[5]Martino D,Joo JE,Sexton-Oates A,et al. Epigenome-wide association study reveals longitudinally stable DNA methylation differences in CD4+T cells from children with Ig E-mediated food allergy[J]. Epigenetics,2014,9(7):998-1006.
[6]Jeffries MA,Dozmorov M,Tang Y,et al. Genome-wide DNA methylation patterns in CD4+T cells from patients with systemic lupus erythematosus[J]. Epigenetics,2011,6(5):593-601.
[7]Barski A,Jothi R,Cuddapah S,et al. Chromatin poises mi RNAand protein-coding genes for expression[J]. Genome Res,2009,19(10):1742-1751.
[8]Han H,Cortez CC,Yang X,et al. DNA methylation directly silences genes with non-CpG island promoters and establishes a nucleosome occupied promoter[J]. Hum Mol Genet,2011,20(22):4299-4310.
[9]Martino D,Maksimovic J,Joo JH,et al. Genome-scale profiling reveals a subset of genes regulated by DNA methylation that program somatic T-cell phenotypes in humans[J]. Genes Immun,2012,13(5):388-398.
[10]Chen K,Xi Y,Pan X,et al. DANPOS:Dynamic analysis of nucleosome position and occupancy by sequencing[J]. Genome Res,2013,23(2):341-351.
[11]Vladimir N,Babenko,Irina V. Chadaeva and Yuriy L. Orlov,Genomic landscape of CpG rich elements in human[J]. BMC Evol Biol,2017,17(1):19.