清华大学颉伟小组取得一项新突破。他们的最新研究提出了染色质结构的建立与胚胎超转录相互作用。相关论文于2025年8月13日发表在《自然》杂志上。

本研究表明，CTCF在母体早期发育过程中占据染色质。相比之下，在单细胞胚胎中，内聚蛋白与染色质结合较差，与TAD溶解一致。从2细胞胚胎到8细胞胚胎，随着TAD的建立，内聚蛋白结合逐渐增加。出乎意料的是，在这一时期，强大的“基因内聚岛”（GCIs）在活性基因的基因体中出现。GCI基因丰富细胞身份和调控基因，在启动子上显示广泛的H3K4me3，并在附近的增强子上表现出与转录因子和黏结蛋白装载器NIPBL的强结合。

该团队发现转录在2到8个细胞的胚胎中是高度活跃的，这是GCI形成所必需的。相反，诱导转录也可以产生GCI。最后，GCI可以作为绝缘边界并与附近的CTCF位点形成接触结构域，从而提高GCI基因的转录水平和稳定性。这些数据揭示了早期胚胎的一种超转录状态，这种状态既塑造了三维基因组组织，也受到了三维基因组组织的促进，揭示了染色质结构和转录之间的密切相互作用。

据悉，受精后，早期胚胎经历常规染色质组织的溶解，包括拓扑相关结构域（TADs）。然后，在三维染色质结构异常缓慢的重新建立过程中，合子基因组开始激活。在早期哺乳动物胚胎中，染色质组织是如何建立的以及它如何与转录相互作用仍然是未知的。

附：英文原文

Title: Establishment of chromatin architecture interplays with embryo hypertranscription

Author: Yu, Guang, Xu, Kai, Xia, Weikun, Zhang, Ke, Xu, Qianhua, Li, Lijia, Lin, Zili, Liu, Ling, Liu, Bofeng, Du, Zhenhai, Chen, Xia, Fan, Qiang, Lai, Fangnong, Wang, Wenying, Wang, Lijuan, Kong, Feng, Wang, Chao, Dai, Haiqiang, Wang, Huili, Xie, Wei

Issue&Volume: 2025-08-13

Abstract: After fertilization, early embryos undergo dissolution of conventional chromatin organization, including topologically associating domains (TADs)1,2. Zygotic genome activation then commences amid unusually slow de novo establishment of three-dimensional chromatin architecture2. How chromatin organization is established and how it interplays with transcription in early mammalian embryos remain elusive. Here we show that CTCF occupies chromatin throughout mouse early development. By contrast, cohesin poorly binds chromatin in one-cell embryos, coinciding with TAD dissolution. Cohesin binding then progressively increases from two- to eight-cell embryos, accompanying TAD establishment. Unexpectedly, strong ‘genic cohesin islands’ (GCIs) emerge across gene bodies of active genes in this period. GCI genes enrich for cell identity and regulatory genes, display broad H3K4me3 at promoters, and exhibit strong binding of transcription factors and the cohesin loader NIPBL at nearby enhancers. We show that transcription is hyperactive in two- to eight-cell embryos and is required for GCI formation. Conversely, induced transcription can also create GCIs. Finally, GCIs can function as insulation boundaries and form contact domains with nearby CTCF sites, enhancing both the transcription levels and stability of GCI genes. These data reveal a hypertranscription state in early embryos that both shapes and is fostered by the three-dimensional genome organization, revealing an intimate interplay between chromatin structure and transcription.

DOI: 10.1038/s41586-025-09400-5

Source: https://www.nature.com/articles/s41586-025-09400-5