Natural Antisense Transcript PEBP1P3 Regulates the RNA Expression, DNA Methylation and Histone Modification of CD45 Gene.
Natural Antisense Transcript PEBP1P3 Regulates the RNA Expression, DNA Methylation and Histone Modification of CD45 Gene.
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天然反义转录本PEBP1P3调节CD45基因的RNA表达、DNA甲基化和组蛋白修饰
DOI：
10.3390/genes12050759
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发表时间：
2021-05-17
期刊：
影响因子：
3.5
通讯作者：
Huang D
中科院分区：
文献类型：
--
作者：
Su Z;Liu G;Zhang B;Lin Z;Huang D
白细胞共同抗原CD 45是一种跨膜磷酸酶，表达于所有有核造血细胞上，其剪接异构体的表达水平与淋巴细胞的发育和功能密切相关。PEBP 1 P3是来自CD 45内含子2的相对链的天然反义转录物，并且被预测为非编码RNA。基因型-组织表达和定量PCR数据表明PEBP 1 P3可能参与调节CD 45剪接异构体的表达。为探讨PEBP 1 P3对CD 45表达的调控机制，分别采用硫酸氢盐测序PCR和染色质免疫沉淀法检测DNA甲基化和组蛋白修饰。结果表明，反义RNA PEBP 1 P3被RNA干扰敲低后，CD 45内含子2的DNA甲基化水平降低，组蛋白H3 K9和H3 K36的三甲基化水平升高。PEBP 1 P3的敲低也增加了染色质构象组织者CTCF在内含子2和CD 45的选择性剪接外显子的结合水平。结果表明，天然反义RNA PEBP 1 P3调控CD 45 RNA的选择性剪接，并可能与组蛋白修饰和DNA甲基化调控有关。
The leukocyte common antigen CD45 is a transmembrane phosphatase expressed on all nucleated hemopoietic cells, and the expression levels of its splicing isoforms are closely related to the development and function of lymphocytes. PEBP1P3 is a natural antisense transcript from the opposite strand of CD45 intron 2 and is predicted to be a noncoding RNA. The genotype-tissue expression and quantitative PCR data suggested that PEBP1P3 might be involved in the regulation of expression of CD45 splicing isoforms. To explore the regulatory mechanism of PEBP1P3 in CD45 expression, DNA methylation and histone modification were detected by bisulfate sequencing PCR and chromatin immunoprecipitation assays, respectively. The results showed that after the antisense RNA PEBP1P3 was knocked down by RNA interference, the DNA methylation of CD45 intron 2 was decreased and histone H3K9 and H3K36 trimethylation at the alternative splicing exons of CD45 DNA was increased. Knockdown of PEBP1P3 also increased the binding levels of chromatin conformation organizer CTCF at intron 2 and the alternative splicing exons of CD45. The present results indicate that the natural antisense RNA PEBP1P3 regulated the alternative splicing of CD45 RNA, and that might be correlated with the regulation of histone modification and DNA methylation.
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影响因子：
30.5
作者：
Chang VT;Fernandes RA;Ganzinger KA;Lee SF;Siebold C;McColl J;Jönsson P;Palayret M;Harlos K;Coles CH;Jones EY;Lui Y;Huang E;Gilbert RJC;Klenerman D;Aricescu AR;Davis SJ
通讯作者：
Davis SJ
影响因子：
64.5
作者：
Luco RF;Allo M;Schor IE;Kornblihtt AR;Misteli T
通讯作者：
Misteli T
影响因子：
30.8
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通讯作者：
Moore, Helen F.
影响因子：
14.9
作者：
Preussner M;Schreiner S;Hung LH;Porstner M;Jäck HM;Benes V;Rätsch G;Bindereif A
通讯作者：
Bindereif A
影响因子：
7.3
作者：
Courtney, Adam H.;Shvets, Alexey A.;Weiss, Arthur
通讯作者：
Weiss, Arthur