Center for Stem Cell Biology and Regenerative Medicine, MOE Key Laboratory of Bioinformatics, New Cornerstone Science Laboratory, School of Life Sciences, Tsinghua University, Beijing, China.
Tsinghua-Peking Center for Life Sciences, Beijing, China.
Nat Cell Biol. 2024 Jun;26(6):962-974. doi: 10.1038/s41556-024-01422-x. Epub 2024 Jun 5.
Dynamic epigenomic reprogramming occurs during mammalian oocyte maturation and early development. However, the underlying transcription circuitry remains poorly characterized. By mapping cis-regulatory elements using H3K27ac, we identified putative enhancers in mouse oocytes and early embryos distinct from those in adult tissues, enabling global transitions of regulatory landscapes around fertilization and implantation. Gene deserts harbour prevalent putative enhancers in fully grown oocytes linked to oocyte-specific genes and repeat activation. Embryo-specific enhancers are primed before zygotic genome activation and are restricted by oocyte-inherited H3K27me3. Putative enhancers in oocytes often manifest H3K4me3, bidirectional transcription, Pol II binding and can drive transcription in STARR-seq and a reporter assay. Finally, motif analysis of these elements identified crucial regulators of oogenesis, TCF3 and TCF12, the deficiency of which impairs activation of key oocyte genes and folliculogenesis. These data reveal distinctive regulatory landscapes and their interacting transcription factors that underpin the development of mammalian oocytes and early embryos.
哺乳动物卵母细胞成熟和早期发育过程中会发生动态表观遗传重编程。然而，其潜在的转录调控回路仍未被很好地描述。通过使用 H3K27ac 来绘制顺式调控元件，我们在小鼠卵母细胞和早期胚胎中鉴定出了与成体组织不同的潜在增强子，从而实现了受精和着床前后调控景观的全面转变。在完全成熟的卵母细胞中，基因荒漠中普遍存在与卵母细胞特异性基因和重复激活相关的潜在增强子。胚胎特异性增强子在合子基因组激活之前就已经被预先激活，并受到卵母细胞遗传的 H3K27me3 的限制。卵母细胞中的潜在增强子通常表现出 H3K4me3、双向转录、Pol II 结合，并可以在 STARR-seq 和报告基因检测中驱动转录。最后，对这些元件的基序分析鉴定出了卵母细胞发生的关键调控因子 TCF3 和 TCF12，它们的缺乏会损害关键卵母细胞基因的激活和卵泡发生。这些数据揭示了哺乳动物卵母细胞和早期胚胎发育的独特调控景观及其相互作用的转录因子。
