Al Adhami Hala, Bardet Anaïs Flore, Dumas Michael, Cleroux Elouan, Guibert Sylvain, Fauque Patricia, Acloque Hervé, Weber Michael
University of Strasbourg, Strasbourg, France.
CNRS UMR7242, Biotechnology and Cell Signaling, 300 Bd Sébastien Brant, 67412, Illkirch Cedex, France.
BMC Biol. 2022 Mar 23;20(1):70. doi: 10.1186/s12915-022-01270-x.
Cytosine DNA methylation is a heritable epigenetic mark present in most eukaryotic groups. While the patterns and functions of DNA methylation have been extensively studied in mouse and human, their conservation in other vertebrates remains poorly explored. In this study, we interrogated the distribution and function of DNA methylation in primary fibroblasts of seven vertebrate species including bio-medical models and livestock species (human, mouse, rabbit, dog, cow, pig, and chicken).
Our data highlight both divergence and conservation of DNA methylation patterns and functions. We show that the chicken genome is hypomethylated compared to other vertebrates. Furthermore, compared to mouse, other species show a higher frequency of methylation of CpG-rich DNA. We reveal the conservation of large unmethylated valleys and patterns of DNA methylation associated with X-chromosome inactivation through vertebrate evolution and make predictions of conserved sets of imprinted genes across mammals. Finally, using chemical inhibition of DNA methylation, we show that the silencing of germline genes and endogenous retroviruses (ERVs) are conserved functions of DNA methylation in vertebrates.
Our data highlight conserved properties of DNA methylation in vertebrate genomes but at the same time point to differences between mouse and other vertebrate species.
胞嘧啶DNA甲基化是大多数真核生物群体中存在的一种可遗传的表观遗传标记。虽然DNA甲基化的模式和功能已在小鼠和人类中得到广泛研究，但在其他脊椎动物中的保守性仍未得到充分探索。在本研究中，我们研究了包括生物医学模型和家畜物种（人类、小鼠、兔子、狗、牛、猪和鸡）在内的七种脊椎动物原代成纤维细胞中DNA甲基化的分布和功能。
我们的数据突出了DNA甲基化模式和功能的差异与保守性。我们发现与其他脊椎动物相比，鸡基因组的甲基化程度较低。此外，与小鼠相比，其他物种富含CpG的DNA甲基化频率更高。我们揭示了通过脊椎动物进化，大的非甲基化区域以及与X染色体失活相关的DNA甲基化模式的保守性，并预测了跨哺乳动物的保守印记基因集。最后，通过DNA甲基化的化学抑制，我们表明种系基因和内源性逆转录病毒（ERV）的沉默是脊椎动物中DNA甲基化的保守功能。
我们的数据突出了脊椎动物基因组中DNA甲基化的保守特性，但同时也指出了小鼠与其他脊椎动物物种之间的差异。
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