Transposable elements teach T cells new tricks
Transposable elements teach T cells new tricks
复制标题
转座元件教会T细胞新技巧
DOI：
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发表时间：
2020
影响因子：
11.1
通讯作者：
E. Chuong
中科院分区：
文献类型：
--
作者：
A. Ivancevic;E. Chuong
哺乳动物基因组充满了转座元件(TES)：寄生的遗传序列可以在宿主基因组内复制到高拷贝数(1)。TES被广泛认为是细胞类型和上下文特定调控元件的有效来源(2，3)。在PNAS上，Ye等人。(4)分析小鼠CD8+T淋巴细胞的染色质图谱数据，发现多个TE家族对预测的调控序列有贡献。与其他细胞相比，免疫细胞显示TE衍生的增强剂的浓缩程度最高(图1)，这表明TE共选可能优先影响免疫调节网络。
图1.
叶等人(4)观察到免疫基因附近TES的发生率较高。他们假设，小鼠基因组免疫相关区域中TES的丰富使它们能够作为免疫增强剂进行调节共选，潜在地促进了适应性免疫所需的快速调节进化。
转录调控网络是基因表达程序的基础，基因表达程序决定细胞的身份、功能和对刺激的反应。在基因组中，启动子和增强子等调控元件充当了将基因连接到调控网络并控制附近基因表达的“电线”。调控网络的变化被认为是生物体进化的一种重要机制(5)，但推动新的调控因素出现的机制仍然知之甚少。
由于它们在宿主基因组中复制的能力，TES长期以来一直被假设在调节网络的进化中发挥作用(6，7)。虽然大多数TES不再编码功能蛋白，但许多TES保留了转录因子结合位点，从而可以改变附近基因的表达。在过去的十年里，已经有许多研究表征了TES在宿主基因调控中的重要作用(见参考文献)。2)。这些发现指出，TES的共同选择是塑造哺乳动物基因调控网络进化的一般机制。
AS在…上的研究
[↵][1]1可将信件收件人。电子邮件：edward.chuong{at}Colorado.edu。
[1]：#xref-corresp-1-1
Mammalian genomes are replete with transposable elements (TEs): parasitic genetic sequences that can replicate to high copy numbers within host genomes (1). TEs are widely recognized as a potent source of cell type- and context-specific regulatory elements (2, 3). In PNAS, Ye et al. (4) analyze chromatin profiling data from mouse CD8+ T lymphocytes and find that multiple TE families contribute to predicted regulatory sequences. Compared to other cells, immune cells show the highest enrichment of TE-derived enhancers (Fig. 1), suggesting that TE cooption may preferentially influence immune regulatory networks.
Fig. 1.
Ye et al. (4) observe higher occurrences of TEs near immune genes. They hypothesize that the abundance of TEs in immune-associated regions of the mouse genome has enabled their regulatory cooption as immune enhancers, potentially facilitating the rapid regulatory evolution needed for adaptive immunity.
Transcriptional regulatory networks underlie the gene expression programs that determine cellular identity, function, and response to stimuli. In the genome, regulatory elements such as promoters and enhancers act as “wires” to connect genes into regulatory networks and control nearby gene expression. Changes to regulatory networks are recognized as an important mechanism for organismal evolution (5), but mechanisms driving the emergence of new regulatory elements are still poorly understood.
Owing to their ability to replicate throughout the host genome, TEs have long been hypothesized to play a role in the evolution of regulatory networks (6, 7). Although most TEs no longer encode functional proteins, many retain transcription factor binding sites and can thus alter the expression of nearby genes. Over the past decade, there have been numerous studies characterizing important roles for TEs in host gene regulation (reviewed in ref. 2). These findings point to the cooption of TEs as a general mechanism shaping the evolution of mammalian gene regulatory networks.
As studies in …
[↵][1]1To whom correspondence may be addressed. Email: edward.chuong{at}colorado.edu.
[1]: #xref-corresp-1-1