Systematic Analysis of Monoallelic Gene Expression and Chromatin Accessibility Across Multiple Tissues in Hybrid Mice.
Systematic Analysis of Monoallelic Gene Expression and Chromatin Accessibility Across Multiple Tissues in Hybrid Mice.
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杂交小鼠多个组织中单等位基因表达和染色质可及性的系统分析
DOI：
10.3389/fcell.2021.717555
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发表时间：
2021
影响因子：
5.5
通讯作者：
Schaefke B
中科院分区：
文献类型：
--
作者：
Liang W;Zou X;Li G;Zhou S;Tian C;Schaefke B
在二倍体真核生物中，通常认为每个常染色体基因的两个等位基因同时以相似的水平表达。然而，一些基因可以优先或严格地从单个等位基因表达，这一过程被称为单等位基因表达。经典的x染色体连锁基因、嗅觉受体基因和发育印迹基因的单等位基因表达是表观遗传修饰的结果。然而，遗传来源依赖的单等位基因表达是由等位基因之间的顺式调控差异引起的。目前缺乏系统的研究来研究这些跨多组织的现象，并且这种单等位基因表达的机制尚未完全了解。在这里，我们提供了在小家鼠菌株C57BL/6J和小家鼠菌株SPRET/EiJ的杂交小鼠中多个组织/细胞系中单等位基因表达的详细描述。我们观察到普遍存在的组织依赖性等位基因特异性基因表达：总共有1839个基因在至少一个组织中表现出单等位基因表达，410个基因在至少两个组织中表现出单等位基因表达。其中88个单等位基因在不同组织间具有不同的活性等位基因，可能代表了基因来源依赖性的单等位基因表达。我们还发现了6个常染色体单等位基因，这些等位基因在所有8个组织中都是相同的，这可能是新的印迹基因候选者。为了描述染色质层的潜在调控机制，我们对来自F1小鼠的两种不同细胞系进行了ATAC-seq。与全球表达模式一致，发现了细胞类型依赖的单等位基因峰，并且在两种细胞类型中都观察到更高比例的C57BL/ 6j活性峰，暗示可能存在物种特异性调控。最后，只有一小部分单等位基因表达可以用启动子区域染色质组织的等位基因差异来解释，这表明其他远端元件可能在塑造等位基因跨组织表达模式中发挥重要作用。
In diploid eukaryotic organisms, both alleles of each autosomal gene are usually assumed to be simultaneously expressed at similar levels. However, some genes can be expressed preferentially or strictly from a single allele, a process known as monoallelic expression. Classic monoallelic expression of X-chromosome-linked genes, olfactory receptor genes and developmentally imprinted genes is the result of epigenetic modifications. Genetic-origin-dependent monoallelic expression, however, is caused by cis-regulatory differences between the alleles. There is a paucity of systematic study to investigate these phenomena across multiple tissues, and the mechanisms underlying such monoallelic expression are not yet fully understood. Here we provide a detailed portrait of monoallelic gene expression across multiple tissues/cell lines in a hybrid mouse cross between the Mus musculus strain C57BL/6J and the Mus spretus strain SPRET/EiJ. We observed pervasive tissue-dependent allele-specific gene expression: in total, 1,839 genes exhibited monoallelic expression in at least one tissue, and 410 genes in at least two tissues. Among these 88 are monoallelic genes with different active alleles between tissues, probably representing genetic-origin-dependent monoallelic expression. We also identified six autosomal monoallelic genes with the active allele being identical in all eight tissues, which are likely novel candidates of imprinted genes. To depict the underlying regulatory mechanisms at the chromatin layer, we performed ATAC-seq in two different cell lines derived from the F1 mouse. Consistent with the global expression pattern, cell-type dependent monoallelic peaks were found, and a higher proportion of C57BL/6J-active peaks were observed in both cell types, implying possible species-specific regulation. Finally, only a small part of monoallelic gene expression could be explained by allelic differences in chromatin organization in promoter regions, suggesting that other distal elements may play important roles in shaping the patterns of allelic gene expression across tissues.
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DOI：
10.1073/pnas.1719138115
发表时间：
2018-04-10
影响因子：
11.1
作者：
Payne JL;Khalid F;Wagner A
通讯作者：
Wagner A
影响因子：
48
作者：
Langmead, Ben;Salzberg, Steven L.
通讯作者：
Salzberg, Steven L.
影响因子：
7
作者：
Emerson, J. J.;Hsieh, Li-Ching;Li, Wen-Hsiung
通讯作者：
Li, Wen-Hsiung
影响因子：
7
作者：
Goncalves A;Leigh-Brown S;Thybert D;Stefflova K;Turro E;Flicek P;Brazma A;Odom DT;Marioni JC
通讯作者：
Marioni JC
影响因子：
--
作者：
Jones, Julie R
通讯作者：
Jones, Julie R