Abstract：
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.
摘要：
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，并在某些情况下导致疾病。然而,L1的调节和功能仍然知之甚少。这里,我们发现L1可以富集RNA聚合酶IIs(RNAPolIIs)，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的L1以抑制RNAPolII富集。RNAPolII转录的急性抑制消除了与L1嵌合转录本相关的结构域边界，表明转录依赖性机制。删除L1会削弱域边界形成，进化过程中的L1插入引入了物种特定的域边界。我们的数据显示，L1可以创建RNAPolII富集区域，从而改变基因组组织，并且SAFB调节L1和RNAPolII活性以保持基因调控。
