CTCF is crucial for chromatin structure and transcription regulation in early embryonic development. However, the kinetics of CTCF chromatin occupation in preimplantation embryos have remained unclear. In this study, we used CUT&RUN technology to investigate CTCF occupancy in mouse preimplantation development. Our findings revealed that CTCF begins binding to the genome prior to zygotic genome activation (ZGA), with a preference for CTCF-anchored chromatin loops. Although the majority of CTCF occupancy is consistently maintained, we identified a specific set of binding sites enriched in the mouse-specific short interspersed element (SINE) family B2 that are restricted to the cleavage stages. Notably, we discovered that the neuroprotective protein ADNP counteracts the stable association of CTCF at SINE B2-derived CTCF-binding sites. Knockout of Adnp in the zygote led to impaired CTCF binding signal recovery, failed deposition of H3K9me3, and transcriptional derepression of SINE B2 during the morula-to-blastocyst transition, which further led to unfaithful cell differentiation in embryos around implantation. Our analysis highlights an ADNP-dependent restriction of CTCF binding during cell differentiation in preimplantation embryos. Furthermore, our findings shed light on the functional importance of transposable elements (TEs) in promoting genetic innovation and actively shaping the early embryo developmental process specific to mammals.

中文翻译：

---

ADNP 在小鼠囊胚形成过程中调节 SINE B2 衍生的 CTCF 结合位点


CTCF 对于早期胚胎发育中的染色质结构和转录调控至关重要。然而，CTCF 染色质在植入前胚胎中占据的动力学仍不清楚。在本研究中，我们使用 CUT&RUN 技术来研究 CTCF 在小鼠植入前发育中的占用情况。我们的研究结果表明，CTCF 在合子基因组激活 (ZGA) 之前开始与基因组结合，并优先选择 CTCF 锚定的染色质环。尽管大多数 CTCF 占据始终保持不变，但我们发现了一组富含小鼠特异性短散布元件 (SINE) 家族 B2 的特定结合位点，这些位点仅限于裂解阶段。值得注意的是，我们发现神经保护蛋白 ADNP 抵消了 CTCF 在 SINE B2 衍生的 CTCF 结合位点上的稳定结合。受精卵中Adnp的敲除导致 CTCF 结合信号恢复受损、H3K9me3 沉积失败以及桑葚胚向囊胚转变期间 SINE B2 的转录去抑制，这进一步导致植入周围胚胎的不忠实细胞分化。我们的分析强调了植入前胚胎细胞分化过程中 CTCF 结合的 ADNP 依赖性限制。此外，我们的研究结果揭示了转座元件（TE）在促进遗传创新和积极塑造哺乳动物特有的早期胚胎发育过程中的功能重要性。