Long interspersed element-1 (LINE-1 or L1) comprises 17% of the human genome, continuously generates genetic variations, and causes disease in certain cases. However, the regulation and function of L1 remain poorly understood. Here, we uncover that L1 can enrich RNA polymerase IIs (RNA Pol IIs), express L1 chimeric transcripts, and create contact domain boundaries in human cells. This impact of L1 is restricted by a nuclear matrix protein scaffold attachment factor B (SAFB) that recognizes transcriptionally active L1s by binding L1 transcripts to inhibit RNA Pol II enrichment. Acute inhibition of RNA Pol II transcription abolishes the domain boundaries associated with L1 chimeric transcripts, indicating a transcription-dependent mechanism. Deleting L1 impairs domain boundary formation, and L1 insertions during evolution have introduced species-specific domain boundaries. Our data show that L1 can create RNA Pol II-enriched regions that alter genome organization and that SAFB regulates L1 and RNA Pol II activity to preserve gene regulation.

长散布元件-1（LINE-1或L1）占人类基因组的17%，不断产生遗传变异，并在某些情况下引起疾病。然而，L1 的调节和功能仍然知之甚少。在这里，我们发现 L1 可以富集 RNA 聚合酶 II (RNA Pol II)、表达 L1 嵌合转录本并在人类细胞中创建接触域边界。 L1 的这种影响受到核基质蛋白支架附着因子 B (SAFB) 的限制，该因子通过结合 L1 转录物来识别转录活性 L1，从而抑制 RNA Pol II 富集。 RNA Pol II 转录的急性抑制消除了与 L1 嵌合转录物相关的结构域边界，表明转录依赖性机制。删除 L1 会损害域边界的形成，而进化过程中 L1 的插入引入了物种特异性的域边界。我们的数据表明，L1 可以创建 RNA Pol II 富集区域，从而改变基因组组织，并且 SAFB 调节 L1 和 RNA Pol II 活性以保持基因调控。