Transposable element-embedded regulatory sequences (TEeRS) and their KRAB-containing zinc finger protein (KZFP) controllers are increasingly recognized as modulators of gene expression. We aim to characterize the contribution of this system to gene regulation in early human development and germ cells. Here, after studying genes driven by the long terminal repeat (LTR) of endogenous retroviruses, we identify the ape-restricted ZNF676 as the sequence-specific repressor of a subset of contemporary LTR12 integrants responsible for a large fraction of transpochimeric gene transcripts (TcGTs) generated during human early embryogenesis. We go on to reveal that the binding of this KZFP correlates with the epigenetic marking of these TEeRS in the germline, and is crucial to the control of genes involved in ciliogenesis/flagellogenesis, a biological process that dates back to the last common ancestor of eukaryotes. These results illustrate how KZFPs and their TE targets contribute to the evolutionary turnover of transcription networks and participate in the transgenerational inheritance of epigenetic traits.

中文翻译：

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KRAB 锌指蛋白 ZNF676 控制 LTR12 相关内源逆转录病毒序列的转录影响

转座元件嵌入调控序列 (TEeRS) 及其包含 KRAB 的锌指蛋白 (KZFP) 控制器越来越被认为是基因表达的调节剂。我们的目标是描述该系统对人类早期发育和生殖细胞基因调控的贡献。在这里，在研究了由内源性逆转录病毒的长末端重复（LTR）驱动的基因后，我们将猿限制性ZNF676鉴定为负责大部分转嵌合基因转录本（TcGT）的当代LTR12整合子子集的序列特异性阻遏物在人类早期胚胎发生过程中产生。我们继续揭示，这种 KZFP 的结合与种系中这些 TEeRS 的表观遗传标记相关，并且对于控制参与纤毛发生/鞭毛发生的基因至关重要，这是一个可以追溯到真核生物最后共同祖先的生物过程。这些结果说明了 KZFP 及其 TE 靶点如何促进转录网络的进化周转并参与表观遗传性状的跨代遗传。