瑞士弗瑞士里德里希·米舍尔生物医学研究所Marc Bühler、Lucas J.T. Kaaij、Fabio Mohn等研究人员发现，ChAHP复合物在SINE扩增来源的CTCF位点抵消染色质环化。2019年9月5日，国际知名学术期刊《细胞》发表了这一成果。

研究人员发现ChAHP复合物（由CHD4、ADNP、HP1组成）与CTCF竞争一组共同的结合模体。在Adnp基因敲除细胞中，在通常由ChAHP结合的位点处形成新的绝缘区域，而近端经典边界则被削弱。这些数据揭示了CTCF介导的DNA环化由不同的锌指蛋白复合物调节。值得注意的是，ChAHP结合的位置主要位于较少分化的SINE B2转座元件中。这表明ChAHP维持进化上保守的空间染色质组织是通过缓冲经过SINE扩增出现的新型CTCF结合位点来实现的。

研究人员表示，CCCTC结合因子（CTCF）和cohesin是三维染色质组织的关键参与者。由CTCF划分的拓扑相关结构域（TAD）在物种之间非常保守，尽管全基因组CTCF结合在转座子介导的模体扩增后基本上变得不同。因此，CTCF共有模体不能很好地预测TAD，并且其他因子必须调节CTCF结合以及随后的TAD形成。

附：英文原文

Title: The ChAHP Complex Counteracts Chromatin Looping at CTCF Sites that Emerged from SINE Expansions in Mouse

Author: Lucas J.T. Kaaij, Fabio Mohn, Robin H. van der Weide, Elzo de Wit, Marc Bühler

Issue&Volume: Volume 178 Issue 6

Abstract: CCCTC-binding factor (CTCF) and cohesin are key players in three-dimensional chromatin organization. The topologically associating domains (TADs) demarcated by CTCF are remarkably well conserved between species, although genome-wide CTCF binding has diverged substantially following transposon-mediated motif expansions. Therefore, the CTCF consensus motif poorly predicts TADs, and additional factors must modulate CTCF binding and subsequent TAD formation. Here, we demonstrate that the ChAHP complex (CHD4, ADNP, HP1) competes with CTCF for a common set of binding motifs. In Adnp knockout cells, novel insulated regions are formed at sites normally bound by ChAHP, whereas proximal canonical boundaries are weakened. These data reveal that CTCF-mediated loop formation is modulated by a distinct zinc-finger protein complex. Strikingly, ChAHP-bound loci are mainly situated within less diverged SINE B2 transposable elements. This implicates ChAHP in maintenance of evolutionarily conserved spatial chromatin organization by buffering novel CTCF binding sites that emerged through SINE expansions.

DOI: 10.1016/j.cell.2019.08.007

Source: https://www.cell.com/cell/fulltext/S0092-8674(19)30895-5