It is now established that Bcl11b specifies T cell fate. Here, we show that in developing T cells, the Bcl11b enhancer repositioned from the lamina to the nuclear interior. Our search for factors that relocalized the Bcl11b enhancer identified a non-coding RNA named ThymoD (thymocyte differentiation factor). ThymoD-deficient mice displayed a block at the onset of T cell development and developed lymphoid malignancies. We found that ThymoD transcription promoted demethylation at CTCF bound sites and activated cohesin-dependent looping to reposition the Bcl11b enhancer from the lamina to the nuclear interior and to juxtapose the Bcl11b enhancer and promoter into a single-loop domain. These large-scale changes in nuclear architecture were associated with the deposition of activating epigenetic marks across the loop domain, plausibly facilitating phase separation. These data indicate how, during developmental progression and tumor suppression, non-coding transcription orchestrates chromatin folding and compartmentalization to direct with high precision enhancer-promoter communication.

中文翻译：

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非编码转录指示染色质折叠和区分开来指导增强子-启动子的通讯和T细胞的命运。

现在确定Bcl11b指定T细胞命运。在这里，我们显示出在发育中的T细胞中，Bcl11b增强子从叶片重新定位到核内部。我们寻找使Bcl11b增强子重新定位的因子，发现了一个非编码RNA，称为ThymoD（胸腺细胞分化因子）。缺乏ThymoD的小鼠在T细胞发育开始时表现出阻断作用，并发展出淋巴样恶性肿瘤。我们发现，ThymoD转录促进CTCF结合位点处的去甲基化并激活黏附素依赖性环，以将Bcl11b增强子从椎板重新定位到核内部，并将Bcl11b增强子和启动子并置为单环结构域。核结构的这些大规模变化与整个环域中活化表观遗传标记的沉积有关，似乎有利于相分离。这些数据表明，在发育进程和肿瘤抑制过程中，非编码转录如何协调染色质折叠和区室化，从而以高精度的增强子-启动子通讯进行引导。