Graduate School of Advanced Science and Engineering, Waseda University, Tokyo, Japan.
Computational Bio Big-Data Open Innovation Laboratory (CBBD-OIL), National Institute of Advanced Industrial Science and Technology (AIST), Tokyo, Japan.
Commun Biol. 2023 Jun 10;6(1):631. doi: 10.1038/s42003-023-04989-7.
Mammalian brains have evolved in stages over a long history to acquire higher functions. Recently, several transposable element (TE) families have been shown to evolve into cis-regulatory elements of brain-specific genes. However, it is not fully understood how TEs are important for gene regulatory networks. Here, we performed a single-cell level analysis using public data of scATAC-seq to discover TE-derived cis-elements that are important for specific cell types. Our results suggest that DNA elements derived from TEs, MER130 and MamRep434, can function as transcription factor-binding sites based on their internal motifs for Neurod2 and Lhx2, respectively, especially in glutamatergic neuronal progenitors. Furthermore, MER130- and MamRep434-derived cis-elements were amplified in the ancestors of Amniota and Eutheria, respectively. These results suggest that the acquisition of cis-elements with TEs occurred in different stages during evolution and may contribute to the acquisition of different functions or morphologies in the brain.
哺乳动物大脑在漫长的历史中经历了多个阶段的进化，从而获得了更高的功能。最近，已经有几个转座元件（TE）家族被证明可以进化为大脑特异性基因的顺式调控元件。然而，TE 对于基因调控网络的重要性还不完全清楚。在这里，我们使用 scATAC-seq 的公共数据进行了单细胞水平的分析，以发现对特定细胞类型重要的 TE 衍生顺式元件。我们的结果表明，源自 TE 的 DNA 元件 MER130 和 MamRep434 可以分别基于其内部 Neurod2 和 Lhx2 的基序作为转录因子结合位点发挥作用，特别是在谷氨酸能神经元祖细胞中。此外，MER130 和 MamRep434 衍生的顺式元件分别在羊膜动物和真兽类的祖先中被扩增。这些结果表明，在进化过程中，不同阶段获得了具有 TE 的顺式元件，这可能有助于大脑获得不同的功能或形态。
