B2 SINE Copies Serve as a Transposable Boundary of DNA Methylation and Histone Modifications in the Mouse.
B2 SINE Copies Serve as a Transposable Boundary of DNA Methylation and Histone Modifications in the Mouse.
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DOI：
10.1093/molbev/msab033
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发表时间：
2021-05-19
影响因子：
10.7
通讯作者：
Ichiyanagi K
中科院分区：
文献类型：
--
作者：
Ichiyanagi T;Katoh H;Mori Y;Hirafuku K;Boyboy BA;Kawase M;Ichiyanagi K
哺乳动物基因组中，特别是在基因丰富的基因组区域中，存在超过一百万个拷贝的短散布元件（SINE）（一类反转录转座子）。越来越多的证据表明，古老的 SINE 序列通过逆转录转座后的多次突变获得了新的转录因子 (TF) 结合位点，从而在进化过程中重新连接了宿主调控网络。然而，目前尚不清楚当前活跃的 SINE 是否有助于 TF 结合位点的扩展。为了研究 SINE 拷贝的迁移性、表达和功能，我们首先鉴定了小家鼠 (Mus musculus) 中约 2,000 个 SINE B1 和 B2 家族的插入多态性。使用一种名为 melRNA-seq 的新型 RNA 测序方法，我们在亚科和基因组拷贝水平上检测了雄性生殖细胞中 SINE 的表达：绝大多数 B1 RNA 起源于进化上年轻的亚科，而 B2 RNA 起源于年轻和年老的亚科。肝脏中的 DNA 甲基化和染色质免疫沉淀测序 (ChIP-seq) 分析表明，多态性 B2 插入作为边界元件抑制 DNA 低甲基化和组蛋白高乙酰化区域的扩展，并降低邻近基因的表达。此外，基因组 B2 拷贝在各种组蛋白修饰的边界处富集，染色质绝缘子蛋白 CCCTC 结合因子（一种众所周知的染色质边界蛋白）与 >100 个多态性和 >10,000 个非多态性 B2 插入结合。这些结果表明，当前活跃的 B2 拷贝是可调节染色质修饰和基因表达的移动边界元件，并且可能参与小鼠物种的表观基因组和表型多样化。
More than one million copies of short interspersed elements (SINEs), a class of retrotransposons, are present in the mammalian genomes, particularly within gene-rich genomic regions. Evidence has accumulated that ancient SINE sequences have acquired new binding sites for transcription factors (TFs) through multiple mutations following retrotransposition, and as a result have rewired the host regulatory network during the course of evolution. However, it remains unclear whether currently active SINEs contribute to the expansion of TF binding sites. To study the mobility, expression, and function of SINE copies, we first identified about 2,000 insertional polymorphisms of SINE B1 and B2 families within Mus musculus. Using a novel RNA sequencing method designated as melRNA-seq, we detected the expression of SINEs in male germ cells at both the subfamily and genomic copy levels: the vast majority of B1 RNAs originated from evolutionarily young subfamilies, whereas B2 RNAs originated from both young and old subfamilies. DNA methylation and chromatin immunoprecipitation-sequencing (ChIP-seq) analyses in liver revealed that polymorphic B2 insertions served as a boundary element inhibiting the expansion of DNA hypomethylated and histone hyperacetylated regions, and decreased the expression of neighboring genes. Moreover, genomic B2 copies were enriched at the boundary of various histone modifications, and chromatin insulator protein, CCCTC-binding factor, a well-known chromatin boundary protein, bound to >100 polymorphic and >10,000 non-polymorphic B2 insertions. These results suggest that the currently active B2 copies are mobile boundary elements that can modulate chromatin modifications and gene expression, and are likely involved in epigenomic and phenotypic diversification of the mouse species.
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