ArticleGenome biology2020
Cis-acting lnc-eRNA SEELA directly binds histone H4 to promote histone recognition and leukemia progression.
Article in Genome biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 25 citations in OpenAlex.
- A thioredoxin-Serinc2-lipid signaling axis modulates mood-related behaviors in mice.Molecular psychiatry · 2026Article
- The hidden regulators: Non-coding RNAs in KMT2A-rearranged acute lymphoblastic leukemia.International journal of cancer · 2026Review
- RBM15B recognizes H3K79me2 to guide selective mThe EMBO journal · 2026Article
- Deciphering the regulatory landscape of enhancer RNAs in health and disease.Signal transduction and targeted therapy · 2026Review
- Emerging insights into enhancer RNAs: biogenesis, function, mechanism, and disease implication.Briefings in bioinformatics · 2026Review
- The antisense lncRNA of TAB2 that prevents oxidative stress to enhance the follicular growth in mammals.Communications biology · 2024Article
- Serinc2 Drives the Progression of Cervical Cancer Through Regulating Myc Pathway.Cancer medicine · 2024Article
- Hypoxia and low-glucose environments co-induced HGDILnc1 promote glycolysis and angiogenesis.Cell death discovery · 2024Article
- Crosstalk between Noncoding RNAs and the Epigenetics Machinery in Pediatric Tumors and Their Microenvironment.Cancers · 2023Review
- METTL3 protects METTL14 from STUB1-mediated degradation to maintain mEMBO reports · 2023Article
- Roles of super enhancers and enhancer RNAs in skeletal muscle development and disease.Cell cycle (Georgetown, Tex.) · 2023Review
- Identification of novel prognostic biomarkers in the TF-enhancer-target regulatory network in hepatocellular carcinoma and immune infiltration analysis.Frontiers in genetics · 2023Article
- Article
- Exploring the potential of eRNAs in cancer immunotherapy.Molecular therapy oncolytics · 2022Article
- The roles and mechanisms of the lncRNA-miRNA axis in the progression of esophageal cancer: a narrative review.Journal of thoracic disease · 2022Review
- The snoRNA-like lncRNA LNC-SNO49AB drives leukemia by activating the RNA-editing enzyme ADAR1.Cell discovery · 2022Article
- Long non‑coding RNAs interact with RNA‑binding proteins to regulate genomic instability in cancer cells (Review).Oncology reports · 2022Review
- Review
- Inflammatory Immune-Associated eRNA: Mechanisms, Functions and Therapeutic Prospects.Frontiers in immunology · 2022Review
- The Emerging Role of the Serine Incorporator Protein Family in Regulating Viral Infection.Frontiers in cell and developmental biology · 2022Review
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundLong noncoding enhancer RNAs (lnc-eRNAs) are a subset of stable eRNAs identified from annotated lncRNAs. They might act as enhancer activity-related therapeutic targets in cancer. However, the underlying mechanism of epigenetic activation and their function in cancer initiation and progression remain largely unknown.
resultsWe identify a set of lncRNAs as lnc-eRNAs according to the epigenetic signatures of enhancers. We show that these lnc-eRNAs are broadly activated in MLL-rearranged leukemia (MLL leukemia), an aggressive leukemia caused by a chromosomal translocation, through a mechanism by which the HOXA cluster initiates enhancer activity, and the epigenetic reader BRD4 cooperates with the coregulator MLL fusion oncoprotein to induce transcriptional activation. To demonstrate the functional roles of lnc-eRNAs, two newly identified lnc-eRNAs transcribed from the SEELA eRNA cluster (SEELA), SEELA1 and SEELA2, are chosen for further studies. The results show that SEELA mediated cis-activated transcription of the nearby oncogene Serine incorporate 2 (SERINC2) by directly binding to the K31 amino acid (aa) of histone H4. Chromatin-bound SEELA strengthens the interaction between chromatin and histone modifiers to promote histone recognition and oncogene transcription. Further studies show that the SEELA-SERINC2 axis regulated aspects of cancer metabolism, such as sphingolipid synthesis, to affect leukemia progression.
conclusionsThis study shows that lnc-eRNAs are epigenetically activated by cancer-initiating oncoproteins and uncovers a cis-activating mechanism of oncogene transcription control based on lnc-eRNA-mediated epigenetic regulation of enhancer activity, providing insights into the critical roles of lnc-eRNAs in cancer initiation and progression.
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