ArticleMolecular cell2022
HOTTIP-dependent R-loop formation regulates CTCF boundary activity and TAD integrity in leukemia.
Article in Molecular cell, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 90 papers, 2 of them syntheses that pooled it.
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Who cites it
90 citing papers in PubMed, 2 syntheses or guidelines pooled it, 146 citations in OpenAlex.
- The role of R-loops-mediated epigenetic regulation in genome stability maintenance and disease pathogenesis: a systematic review.Epigenetics · 2026Pooled it
- Quality-controlled R-loop meta-analysis reveals the characteristics of R-loop consensus regions.Nucleic acids research · 2022Pooled it
- Decoding chromatin-associated RNA (caRNA) interaction networks: from genome-wide dynamic capture to epigenetic mechanisms in plants and animals.Epigenetics · 2026Review
- Genome-wide mapping reveals increased R-loops in topoisomerase III-beta-deficient human cells.iScience · 2026Article
- α-Satellite RNA maintains centromeric cohesion through R-loops.Molecular cell · 2026Article
- Nuclear exosome targeting complexes modulate cohesin binding and enhancer-promoter interactions in 3D.Nature communications · 2026Article
- The role of non-coding RNAs in regulating R-loop dynamics in cancer: Mechanisms and therapeutic implications.Acta pharmaceutica Sinica. B · 2026Review
- Article
- Assessing the contributions of noncoding RNAs in acute myeloid leukemia.Blood neoplasia · 2026Review
- An EGFR co-amplified lncRNA HELDR promotes glioblastoma malignancy through KAT7-driven gene programs.Nature cell biology · 2026Article
- Direct roles of long non-coding RNAs in transcription activation.Nature structural & molecular biology · 2026Review
- Chromatin Accessibility in Cancer: Biological Functions, Mechanisms, Therapeutic Potential, and Future Directions.MedComm · 2026Review
- NPM1c⁺-driven lncRNA dysregulation in AML: Mechanisms, Controversies and translational roadblocks.Translational oncology · 2026Review
- Domestication-Selected Promoter Insertion in WRKY17 Increases Cadmium Sensitivity in Apple.Plant biotechnology journal · 2026Article
- Multi-layered gene regulation by long non-coding RNAs: from chromatin to genome architecture.BMB reports · 2026Review
- USP20, a Super-enhancer Regulated Gene, Promotes Acute Myeloid Leukemia Progression through CTNNB1 Deubiquitination.International journal of biological sciences · 2026Article
- Liuwei Dihuang Prevents Human Umbilical Vein Endothelial Cells SenescenceCombinatorial chemistry & high throughput screening · 2026Article
- The role of R-loop aberrations in lower-grade gliomas: prognostic, immune, and metabolic implications from multi-omics and machine learning analysis.Frontiers in immunology · 2026Article
- Macrophage-derived long non-coding RNAs in cancer: pioneering targets for immune modulation and personalized therapy.Frontiers in immunology · 2026Review
- The METTL3-YTHDC1 axis mediates architectural RNA mMolecular cancer · 2025Article
30 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
19 authors at 6 institutions in 3 countries.
Funding
Abstract
HOTTIP lncRNA is highly expressed in acute myeloid leukemia (AML) driven by MLL rearrangements or NPM1 mutations to mediate HOXA topologically associated domain (TAD) formation and drive aberrant transcription. However, the mechanism through which HOTTIP accesses CCCTC-binding factor (CTCF) chromatin boundaries and regulates CTCF-mediated genome topology remains unknown. Here, we show that HOTTIP directly interacts with and regulates a fraction of CTCF-binding sites (CBSs) in the AML genome by recruiting CTCF/cohesin complex and R-loop-associated regulators to form R-loops. HOTTIP-mediated R-loops reinforce the CTCF boundary and facilitate formation of TADs to drive gene transcription. Either deleting CBS or targeting RNase H to eliminate R-loops in the boundary CBS of β-catenin TAD impaired CTCF boundary activity, inhibited promoter/enhancer interactions, reduced β-catenin target expression, and mitigated leukemogenesis in xenograft mouse models with aberrant HOTTIP expression. Thus, HOTTIP-mediated R-loop formation directly reinforces CTCF chromatin boundary activity and TAD integrity to drive oncogene transcription and leukemia development.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.