Mammalian genomes encode thousands of long noncoding RNAs (lncRNAs), yet the biological functions of most of them remain unknown. A particularly rich repertoire of lncRNAs found in mammalian brain and in the early embryo. We used RNA‐seq and computational analysis to prioritize lncRNAs that may regulate commitment of pluripotent cells to a neuronal fate and perturbed their expression prior to neuronal differentiation. Knockdown by RNAi of two highly conserved and well‐expressed lncRNAs, Reno1 (2810410L24Rik) and lnc‐Nr2f1, decreased the expression of neuronal markers and led to massive changes in gene expression in the differentiated cells. We further show that the Reno1 locus forms increasing spatial contacts during neurogenesis with its adjacent protein‐coding gene Bahcc1. Loss of either Reno1 or Bahcc1 leads to an early arrest in neuronal commitment, failure to induce a neuronal gene expression program, and to global reduction in chromatin accessibility at regions that are marked by the H3K4me3 chromatin mark at the onset of differentiation. Reno1 and Bahcc1 thus form a previously uncharacterized circuit required for the early steps of neuronal commitment.

中文翻译：

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Reno1/Bahcc1 基因座对小鼠胚胎干细胞中神经元定型的调节。

哺乳动物基因组编码数千个长非编码 RNA (lncRNA)，但其中大多数的生物学功能仍然未知。在哺乳动物大脑和早期胚胎中发现的特别丰富的 lncRNA 库。我们使用 RNA-seq 和计算分析来优先考虑可能调节多能细胞对神经元命运的承诺并在神经元分化之前扰乱它们的表达的 lncRNA。通过 RNAi 敲低两种高度保守且表达良好的 lncRNA，Reno1 ( 2810410L24Rik ) 和lnc-Nr2f1，降低了神经元标记物的表达并导致分化细胞中基因表达的巨大变化。我们进一步表明Reno1基因座在神经发生过程中与其相邻的蛋白质编码基因Bahcc1形成越来越多的空间接触。要么丧失Reno1或Bahcc1导致神经元的承诺早日逮捕，不诱导神经元基因表达程序，并在区域中的染色质可访问全球减少了由H3K4me3的染色质标记在分化开始标记。Reno1和 Bahcc1 因此形成了神经元承诺的早期步骤所需的先前未表征的电路。