Kress Clémence, Jouneau Luc, Pain Bertrand
Univ Lyon, Université Lyon 1, INSERM, INRAE, U1208, USC1361, Stem Cell and Brain Research Institute, Bron, France.
Université Paris-Saclay, UVSQ, INRAE, BREED, Jouy-en-Josas, 78350, France.
Epigenetics Chromatin. 2024 Apr 26;17(1):11. doi: 10.1186/s13072-024-00537-7.
In mammals, primordial germ cells (PGCs), the embryonic precursors of the germline, arise from embryonic or extra-embryonic cells upon induction by the surrounding tissues during gastrulation, according to mechanisms which are elucidated in mice but remain controversial in primates. They undergo genome-wide epigenetic reprogramming, consisting of extensive DNA demethylation and histone post-translational modification (PTM) changes, toward a basal, euchromatinized state. In contrast, chicken PGCs are specified by preformation before gastrulation based on maternally-inherited factors. They can be isolated from the bloodstream during their migration to the genital ridges. Our prior research highlighted differences in the global epigenetic profile of cultured chicken PGCs compared with chicken somatic cells and mammalian PGCs. This study investigates the acquisition and evolution of this profile during development.
Quantitative analysis of global DNA methylation and histone PTMs, including their distribution, during key stages of chicken early development revealed divergent PGC epigenetic changes compared with mammals. Unlike mammalian PGCs, chicken PGCs do not undergo genome-wide DNA demethylation or exhibit a decrease in histone H3 lysine 9 dimethylation. However, chicken PGCs show 5‑hydroxymethylcytosine loss, macroH2A redistribution, and chromatin decompaction, mirroring mammalian processes. Chicken PGCs initiate their epigenetic signature during migration, progressively accumulating high global levels of H3K9me3, with preferential enrichment in inactive genome regions. Despite apparent global chromatin decompaction, abundant heterochromatin marks, including repressive histone PTMs, HP1 variants, and DNA methylation, persists in chicken PGCs, contrasting with mammalian PGCs.
Chicken PGCs' epigenetic signature does not align with the basal chromatin state observed in mammals, suggesting a departure from extensive epigenetic reprogramming. Despite disparities in early PGC development, the persistence of several epigenetic features shared with mammals implies their involvement in chromatin-regulated germ cell properties, with the distinctive elevation of chicken-specific H3K9me3 potentially participating in these processes.
在哺乳动物中，原始生殖细胞（PGCs）作为生殖系的胚胎前体，在原肠胚形成过程中，由周围组织诱导胚胎或胚外细胞产生，其机制在小鼠中已得到阐明，但在灵长类动物中仍存在争议。它们经历全基因组表观遗传重编程，包括广泛的DNA去甲基化和组蛋白翻译后修饰（PTM）变化，转变为基础的、常染色质化状态。相比之下，鸡的PGCs在原肠胚形成前基于母系遗传因素预先形成。在它们迁移到生殖嵴的过程中，可以从血液中分离出来。我们之前的研究强调了培养的鸡PGCs与鸡体细胞和哺乳动物PGCs在整体表观遗传特征上的差异。本研究调查了这种特征在发育过程中的获得和演变。
对鸡早期发育关键阶段的全基因组DNA甲基化和组蛋白PTM进行定量分析，包括它们的分布，结果显示与哺乳动物相比，鸡PGCs的表观遗传变化存在差异。与哺乳动物PGCs不同，鸡PGCs不会经历全基因组DNA去甲基化，也不会表现出组蛋白H3赖氨酸9二甲基化的减少。然而，鸡PGCs表现出5-羟甲基胞嘧啶的丢失、macroH2A的重新分布以及染色质解压缩，这与哺乳动物的过程相似。鸡PGCs在迁移过程中开始其表观遗传特征，逐渐积累高水平的全基因组H3K9me3，并优先富集在非活性基因组区域。尽管表观上整体染色质解压缩，但与哺乳动物PGCs不同，鸡PGCs中仍存在大量异染色质标记，包括抑制性组蛋白PTM、HP1变体和DNA甲基化。
鸡PGCs的表观遗传特征与在哺乳动物中观察到的基础染色质状态不一致，这表明其偏离了广泛的表观遗传重编程。尽管PGCs早期发育存在差异，但与哺乳动物共有的几种表观遗传特征的持续存在意味着它们参与了染色质调节的生殖细胞特性，鸡特异性H3K9me3的独特升高可能参与了这些过程。
