| 描述信息 |
Long interspersed element-1 (LINE-1, also known as L1) accounts for 17% of human genome and exhibits varied transcription activities in development and disease. But, the regulation and function of L1 transcription remain incompletely understood. Through genome-wide CRISPR/Cas9 screening against one reporter driven by L1 5 UTR, we identified functionally diverse genes in control of L1 transcription, as well as the function of L1 in long-range gene activation. Systematic activation/silencing of L1s en masse via CRISPRa/i significantly up-/down-regulates expression of widespread genes over long genomic distances, respectively. Transcriptional activation of L1s facilitates the physical contacts between L1s and their cognate genes, which can get disrupted when L1s are silenced. While genetic deletion of L1 decreases its cognate gene expression, L1 insertions in the hominin lineage over the past 15 million years appear to booster zygotic genome activation in primates. Overall, our results illustrate the regulation and function of pervasive L1s in activating long-range gene expression. |
