TRIM28 在人神经祖细胞中控制基于内源性逆转录病毒的基因调控网络。
TRIM28 Controls a Gene Regulatory Network Based on Endogenous Retroviruses in Human Neural Progenitor Cells.
机构信息
Laboratory of Molecular Neurogenetics, Department of Experimental Medical Science, Wallenberg Neuroscience Center and Lund Stem Cell Center, BMC A11, Lund University, 221 84 Lund, Sweden.
Developmental and Regenerative Neurobiology, Department of Experimental Medical Science, Wallenberg Neuroscience Center and Lund Stem Cell Center, BMC A11, Lund University, 221 84 Lund, Sweden.
出版信息
Cell Rep. 2017 Jan 3;18(1):1-11. doi: 10.1016/j.celrep.2016.12.010.
Endogenous retroviruses (ERVs), which make up 8% of the human genome, have been proposed to participate in the control of gene regulatory networks. In this study, we find a region- and developmental stage-specific expression pattern of ERVs in the developing human brain, which is linked to a transcriptional network based on ERVs. We demonstrate that almost 10,000, primarily primate-specific, ERVs act as docking platforms for the co-repressor protein TRIM28 in human neural progenitor cells, which results in the establishment of local heterochromatin. Thereby, TRIM28 represses ERVs and consequently regulates the expression of neighboring genes. These results uncover a gene regulatory network based on ERVs that participates in control of gene expression of protein-coding transcripts important for brain development.
内源性逆转录病毒（ERVs）占人类基因组的 8%，据推测它们参与了基因调控网络的控制。在这项研究中，我们发现 ERVs 在人类大脑发育过程中有一个区域和发育阶段特异性的表达模式，该模式与基于 ERVs 的转录网络有关。我们证明，近 10000 个主要是灵长类特异性的 ERVs 可作为人类神经祖细胞中辅抑制蛋白 TRIM28 的 docking 平台，从而导致局部异染色质的建立。由此，TRIM28 抑制 ERVs，进而调节邻近基因的表达。这些结果揭示了一个基于 ERVs 的基因调控网络，它参与调控对大脑发育重要的蛋白质编码转录本的基因表达。
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