中国科学院广州生物医药与健康研究院姚红杰小组的研究解析CTCF和CTCF-s在人胚胎干细胞中的功能作用。2025年12月23日，国际知名学术期刊《遗传学报》发表了这一成果。

在这项研究中，课题组研究人员将生长素诱导的degron （AID2）系统与多西环素诱导的转基因表达进行了主题化，系统地研究了CTCF和CTCF-s在人胚胎干细胞（hESCs）中的作用。内源性CTCF和CTCF-s的急性降解，以及随后的同种异型特异性修复，表明CTCF对细胞形态和增殖至关重要，而CTCF-s的作用要弱得多。全基因组ChIP-seq和Hi-C分析揭示了CTCF和CTCF-s不同的结合景观，以及它们对染色质构象的不同贡献。值得注意的是，他们的数据表明，CTCF-s和CTCF一样，既可以作为边界绝缘体，也可以结合基因启动子来调节一部分基因的表达。总的来说，他们的研究表明CTCF在调节染色质边界稳定性和基因调控方面占主导地位，而CTCF-s的作用较小。

据介绍，CTCF是一种高度保守的锌指蛋白，在转录调控和三维基因组组织中起着关键作用。CTCF的另一种剪接异构体（CTCF-s）缺乏N端结构域和2.5个锌指，与CTCF竞争基因组占用并减少CTCF介导的染色质相互作用。然而，CTCF和CTCF-s之间的功能差异尚不清楚。

附：英文原文

Title: Dissecting the functional roles of CTCF and CTCF-s in human embryonic stem cells

Author: Hongjie Yao a b c

Issue&Volume: 2025/12/23

Abstract: CTCF is a highly conserved zinc finger protein that plays critical roles in transcriptional regulation and three-dimensional (3D) genome organization. An alternative splice isoform of CTCF (CTCF-s), lacking the N-terminal domain and 2.5 zinc fingers, competes with CTCF for genomic occupancy and reduces CTCF-mediated chromatin interactions. However, the functional differences between CTCF and CTCF-s remain unclear. In this study, by using an auxin-inducible degron (AID2) system with doxycycline-inducible transgene expression, we systematically investigate the roles of CTCF and CTCF-s in human embryonic stem cells (hESCs). Acute degradation of endogenous CTCF and CTCF-s, followed by isoform-specific rescue, reveals that CTCF is essential for cell morphology and proliferation, whereas CTCF-s exerts much weaker effects. Genome-wide ChIP-seq and Hi-C analysis uncover distinct binding landscapes for CTCF and CTCF-s, as well as their differential contributions to chromatin conformation. Notably, our data indicate that CTCF-s, like CTCF, could either act as a boundary insulator or bind to gene promoters to modulate expression of a fraction of genes. Overall, our study reveals that CTCF is dominant in regulating chromatin boundary stability and gene regulation, while CTCF-s contributes to a lesser degree.

DOI: 10.1016/j.jgg.2025.12.007

Source: https://www.sciencedirect.com/science/article/abs/pii/S1673852725003492