Analysis of epigenetic features characteristic of L1 loci expressed in human cells.
Analysis of epigenetic features characteristic of L1 loci expressed in human cells.
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DOI：
10.1093/nar/gkac013
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发表时间：
2022-02-28
影响因子：
14.9
通讯作者：
Belancio VP
中科院分区：
文献类型：
--
作者：
Freeman B;White T;Kaul T;Stow EC;Baddoo M;Ungerleider N;Morales M;Yang H;Deharo D;Deininger P;Belancio VP
人类基因组中只有少数L1基因座在任何给定的细胞系或器官中表达，这可能会使对基因组的损害最小化。表观遗传的特点和要求的表达L1基因座目前是未知的。使用人类细胞和全面的表观遗传分析的个人表达和未表达的L1基因座，我们确定内源性L1转录取决于表观遗传因素的组合，包括开放的染色质，激活组蛋白修饰，并在L1启动子低甲基化。我们证明，L1启动子似乎需要与增强子元件的相互作用，以实现最佳功能。我们利用表观遗传背景来预测L1 Hs基因座的表达状态，这些基因座用RNA-Seq难以定位。我们的分析确定了一群“过渡性”L1基因座，它们可能在肿瘤和衰老过程中观察到的表观遗传失调期间具有更大的激活潜力，因为它们对靶向CRISPR介导的反式激活结构域的递送反应最灵敏。我们证明，内源性L1 mRNA表达的工程增加增加铝动员。总的来说，我们的研究结果提出了第一个全球性的和全面的分析表观遗传状态的个人L1基因座的基础上，他们的表达状态，并证明表观遗传背景的重要性L1表达异质性。
Only a select few L1 loci in the human genome are expressed in any given cell line or organ, likely to minimize damage done to the genome. The epigenetic features and requirements of expressed L1 loci are currently unknown. Using human cells and comprehensive epigenetic analysis of individual expressed and unexpressed L1 loci, we determined that endogenous L1 transcription depends on a combination of epigenetic factors, including open chromatin, activating histone modifications, and hypomethylation at the L1 promoter. We demonstrate that the L1 promoter seems to require interaction with enhancer elements for optimal function. We utilize epigenetic context to predict the expression status of L1Hs loci that are poorly mappable with RNA-Seq. Our analysis identified a population of ‘transitional’ L1 loci that likely have greater potential to be activated during the epigenetic dysregulation seen in tumors and during aging because they are the most responsive to targeted CRISPR-mediated delivery of trans-activating domains. We demonstrate that an engineered increase in endogenous L1 mRNA expression increases Alu mobilization. Overall, our findings present the first global and comprehensive analysis of epigenetic status of individual L1 loci based on their expression status and demonstrate the importance of epigenetic context for L1 expression heterogeneity.
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DOI：
10.1146/annurev-genom-082509-141802
发表时间：
2011
影响因子：
8.7
作者：
Beck CR;Garcia-Perez JL;Badge RM;Moran JV
通讯作者：
Moran JV
LINE-1 RNA剪接和对哺乳动物基因表达的影响。
影响因子：
14.9
作者：
Belancio, VP;Hedges, DJ;Deininger, P
通讯作者：
Deininger, P
影响因子：
14.9
作者：
Belancio VP;Roy-Engel AM;Pochampally RR;Deininger P
通讯作者：
Deininger P
DOI：
10.1073/pnas.0831042100
发表时间：
2003-04-29
影响因子：
11.1
作者：
Brouha, B;Schustak, J;Kazazian, HH
通讯作者：
Kazazian, HH
影响因子：
10.7
作者：
Boissinot, S;Entezam, A;Furano, AV
通讯作者：
Furano, AV