Retrotransposon control in mammals is an intricate process that is effectuated by a broad network of chromatin regulatory pathways. We previously discovered ChAHP, a protein complex with repressive activity against short interspersed element (SINE) retrotransposons that is composed of the transcription factor ADNP, chromatin remodeler CHD4, and HP1 proteins. Here we identify ChAHP2, a protein complex homologous to ChAHP, in which ADNP is replaced by ADNP2. ChAHP2 is predominantly targeted to endogenous retroviruses (ERVs) and long interspersed elements (LINEs) via HP1β-mediated binding of H3K9 trimethylated histones. We further demonstrate that ChAHP also binds these elements in a manner mechanistically equivalent to that of ChAHP2 and distinct from DNA sequence-specific recruitment at SINEs. Genetic ablation of ADNP2 alleviates ERV and LINE1 repression, which is synthetically exacerbated by additional depletion of ADNP. Together, our results reveal that the ChAHP and ChAHP2 complexes function to control both nonautonomous and autonomous retrotransposons by complementary activities, further adding to the complexity of mammalian transposon control.

中文翻译：

---

ChAHP2 和 ChAHP 通过互补活性控制多种反转录转座子


哺乳动物中的逆转录转座子控制是一个复杂的过程，由广泛的染色质调控途径网络实现。我们之前发现了 ChAHP，这是一种对短散布元件 (SINE) 逆转录转座子具有抑制活性的蛋白质复合物，由转录因子 ADNP、染色质重塑蛋白 CHD4 和 HP1 蛋白组成。在这里，我们鉴定了 ChAHP2，一种与 ChAHP 同源的蛋白质复合物，其中 ADNP 被 ADNP2 取代。 ChAHP2 主要通过 HP1β 介导的 H3K9 三甲基化组蛋白结合来靶向内源性逆转录病毒 (ERV) 和长散布元件 (LINE)。我们进一步证明 ChAHP 也以与 ChAHP2 相同的机制结合这些元件，但与 SINE 上 DNA 序列特异性招募不同。 ADNP2 的基因消除可减轻 ERV 和 LINE1 抑制，而 ADNP 的额外消耗会综合加剧这种抑制。总之，我们的结果揭示了 ChAHP 和 ChAHP2 复合物通过互补活性来控制非自主和自主逆转录转座子，进一步增加了哺乳动物转座子控制的复杂性。