Topologically associating domains are disrupted by evolutionary genome rearrangements forming species-specific enhancer connections in mice and humans.
Topologically associating domains are disrupted by evolutionary genome rearrangements forming species-specific enhancer connections in mice and humans.
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拓扑相关结构域被破坏的进化基因组重排形成物种特异性增强子连接在小鼠和人类。
DOI：
10.1016/j.celrep.2022.110769
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发表时间：
2022-05-03
期刊：
影响因子：
8.8
通讯作者：
Weinmann, Amy S.
中科院分区：
文献类型：
--
作者：
Gilbertson, Sarah E.;Walter, Hannah C.;Gardner, Katherine;Wren, Spencer N.;Vahedi, Golnaz;Weinmann, Amy S.
区分保守和不同的调节机制对于将临床前研究从小鼠转化为人类至关重要，但缺乏关于进化基因组重排如何影响免疫反应调节的信息，免疫反应是一个快速进化的系统。目前的模型是拓扑关联结构域（TADs）是保守的物种之间，缓冲进化重排和保存远程相互作用的一个物种。然而，我们发现，TADs经常跨越进化易位和倒位断点附近的基因在免疫细胞中的物种特异性表达，创造独特的增强子-启动子相互作用的小鼠或人类基因组。这包括涵盖免疫相关转录因子、细胞因子和受体的TAD。例如，我们发现了一种进化重排，它在人类巨噬细胞中的OASL和P2 RX 7之间创建了一个共享的LPS诱导的调控模块，而这在小鼠中是不存在的。因此，进化的基因组重排破坏了基因组边界，使物种之间不同基因组位置的序列保守增强子元件能够产生独特的调控模块。目前尚不清楚影响小鼠和人类基因组的进化基因组重排如何影响免疫重要基因的表达。Gilbertson等人报道，进化基因组重排破坏拓扑关联结构域边界，使得来自物种之间不同位置的序列保守增强子元件能够产生独特的调控模块。
Distinguishing between conserved and divergent regulatory mechanisms is essential for translating preclinical research from mice to humans, yet there is a lack of information about how evolutionary genome rearrangements affect the regulation of the immune response, a rapidly evolving system. The current model is topologically associating domains (TADs) are conserved between species, buffering evolutionary rearrangements and conserving long-range interactions within a TAD. However, we find that TADs frequently span evolutionary translocation and inversion breakpoints near genes with species-specific expression in immune cells, creating unique enhancer-promoter interactions exclusive to the mouse or human genomes. This includes TADs encompassing immune-related transcription factors, cytokines, and receptors. For example, we uncover an evolutionary rearrangement that created a shared LPS-inducible regulatory module between OASL and P2RX7 in human macrophages that is absent in mice. Therefore, evolutionary genome rearrangements disrupt TAD boundaries, enabling sequence-conserved enhancer elements from divergent genomic locations between species to create unique regulatory modules. It is currently unclear how evolutionary genome rearrangements affecting the mouse and human genomes influence the expression of genes important in immunity. Gilbertson et al. report that evolutionary genome rearrangements disrupt topologically associating domain boundaries, enabling sequence-conserved enhancer elements from divergent locations between species to create unique regulatory modules.
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影响因子：
9.8
作者：
ENCODE Project Consortium
通讯作者：
ENCODE Project Consortium
胶质瘤干细胞增殖和肿瘤生长由一氧化氮合酶2促进。
影响因子：
64.5
作者：
Eyler CE;Wu Q;Yan K;MacSwords JM;Chandler-Militello D;Misuraca KL;Lathia JD;Forrester MT;Lee J;Stamler JS;Goldman SA;Bredel M;McLendon RE;Sloan AE;Hjelmeland AB;Rich JN
通讯作者：
Rich JN
DOI：
10.4049/jimmunol.1301758
发表时间：
2014-03-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Gross TJ;Kremens K;Powers LS;Brink B;Knutson T;Domann FE;Philibert RA;Milhem MM;Monick MM
通讯作者：
Monick MM
影响因子：
64.8
作者：
Fritz, Joerg H.;Rojas, Olga Lucia;Simard, Nathalie;McCarthy, Douglas D.;Hapfelmeier, Siegfried;Rubino, Stephen;Robertson, Susan J.;Larijani, Mani;Gosselin, Jean;Ivanov, Ivaylo I.;Martin, Alberto;Casellas, Rafael;Philpott, Dana J.;Girardin, Stephen E.;McCoy, Kathy D.;Macpherson, Andrew J.;Paige, Christopher J.;Gommerman, Jennifer L.
通讯作者：
Gommerman, Jennifer L.
影响因子：
7
作者：
Bourque, G;Pevzner, PA;Tesler, G
通讯作者：
Tesler, G