Confinement of the X chromosome to a territory for dosage compensation is a prime example of how subnuclear compartmentalization is used to regulate transcription at the megabase scale. In Drosophila melanogaster , two sex-specific non-coding RNAs (roX1 and roX2) are transcribed from the X chromosome. They associate with the male-specific lethal (MSL) complex 1 , which acetylates histone H4 lysine 16 and thereby induces an approximately twofold increase in expression of male X-linked genes 2 , 3 . Current models suggest that X-over-autosome specificity is achieved by the recognition of cis -regulatory DNA high-affinity sites (HAS) by the MSL2 subunit 4 , 5 . However, HAS motifs are also found on autosomes, indicating that additional factors must stabilize the association of the MSL complex with the X chromosome. Here we show that the low-complexity C-terminal domain (CTD) of MSL2 renders its recruitment to the X chromosome sensitive to roX non-coding RNAs. roX non-coding RNAs and the MSL2 CTD form a stably condensed state, and functional analyses in Drosophila and mammalian cells show that their interactions are crucial for dosage compensation in vivo. Replacing the CTD of mammalian MSL2 with that from Drosophila and expressing roX in cis is sufficient to nucleate ectopic dosage compensation in mammalian cells. Thus, the condensing nature of roX–MSL2 CTD is the primary determinant for specific compartmentalization of the X chromosome in Drosophila . Dosage compensation in Drosophila involves nucleation of the dosage compensation complex at the X chromosome by MSL2 and the non-coding RNA roX.

中文翻译：

---

MSL2的RNA成核诱导选择性X染色体区室化

将 X 染色体限制在剂量补偿区域是如何使用亚核区室化来调节兆碱基规模转录的一个主要例子。在黑腹果蝇中，两个性别特异性非编码 RNA（roX1 和 roX2）从 X 染色体转录。它们与雄性特异性致死 (MSL) 复合物 1 相关，该复合物使组蛋白 H4 赖氨酸 16 乙酰化，从而诱导雄性 X 连锁基因 2、3 的表达增加约两倍。目前的模型表明，X-over-autosome 特异性是通过 MSL2 亚基 4、5 识别顺式调节 DNA 高亲和力位点 (HAS) 来实现的。然而，在常染色体上也发现了 HAS 基序，这表明其他因素必须稳定 MSL 复合体与 X 染色体的关联。在这里，我们表明 MSL2 的低复杂性 C 末端结构域 (CTD) 使其募集到对 roX 非编码 RNA 敏感的 X 染色体。roX 非编码 RNA 和 MSL2 CTD 形成稳定的凝聚态，果蝇和哺乳动物细胞的功能分析表明，它们的相互作用对于体内剂量补偿至关重要。用来自果蝇的 CTD 替换哺乳动物 MSL2 的 CTD 并在 cis 中表达 roX 足以使哺乳动物细胞中的异位剂量补偿成核。因此，roX-MSL2 CTD 的凝聚性质是果蝇 X 染色体特定区室化的主要决定因素。果蝇中的剂量补偿涉及 MSL2 和非编码 RNA roX 在 X 染色体上剂量补偿复合物的成核。