ArticleNucleic acids research2021
A functional LSD1 coregulator screen reveals a novel transcriptional regulatory cascade connecting R-loop homeostasis with epigenetic regulation.
Article in Nucleic acids research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 42 citations in OpenAlex.
- The novel tertiary amine LSD1 inhibitor 596 inhibits endometrial cancer through the mTOR signal transduction pathway.Translational oncology · 2026Article
- A synergistic interaction between PRMT5 and LSD1 inhibitors in AML.Science advances · 2026Article
- Targeting R-loops: diverse RNA helicases in R-loop resolution and their potential as targets for cancer therapy.Frontiers in cell and developmental biology · 2026Review
- Inhibition of LSD1 enhances T cells anti-tumor immunity by promoting TNFSF14 expression in gastric cancer.Molecular and cellular biochemistry · 2026Article
- Article
- CRISPR GENome and epigenome engineering improves loss-of-function genetic-screening approaches.Cell reports methods · 2025Article
- Identification of FLYWCH1 as a regulator of platinum-resistance in epithelial ovarian cancer.NAR cancer · 2025Article
- The kinase NEK6 positively regulates LSD1 activity and accumulation in local chromatin sub-compartments.Communications biology · 2024Article
- A CPF-like phosphatase module links transcription termination to chromatin silencing.Molecular cell · 2024Article
- TERRA-LSD1 phase separation promotes R-loop formation for telomere maintenance in ALT cancer cells.Nature communications · 2024Article
- Kdm1a safeguards the topological boundaries of PRC2-repressed genes and prevents aging-related euchromatinization in neurons.Nature communications · 2024Article
- Fluorescent Reporter Systems to Investigate Chromatin Effector Proteins in Living Cells.Methods in molecular biology (Clifton, N.J.) · 2024Article
- LSD1: an emerging face in altering the tumor microenvironment and enhancing immune checkpoint therapy.Journal of biomedical science · 2023Review
- H3K27me3-H3K4me1 transition at bivalent promoters instructs lineage specification in development.Cell & bioscience · 2023Article
- The MECP2-TRD domain interacts with the DNMT3A-ADD domain at the H3-tail binding site.Protein science : a publication of the Protein Society · 2023Article
- R-loop Mapping and Characterization During Drosophila Embryogenesis Reveals Developmental Plasticity in R-loop Signatures.Journal of molecular biology · 2022Article
- Article
- The intersection of DNA replication with antisense 3' RNA processing inProceedings of the National Academy of Sciences of the United States of America · 2021Article
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The lysine specific demethylase 1 (LSD1) plays a pivotal role in cellular differentiation by regulating the expression of key developmental genes in concert with different coregulatory proteins. This process is impaired in different cancer types and incompletely understood. To comprehensively identify functional coregulators of LSD1, we established a novel tractable fluorescent reporter system to monitor LSD1 activity in living cells. Combining this reporter system with a state-of-the-art multiplexed RNAi screen, we identify the DEAD-box helicase 19A (DDX19A) as a novel coregulator and demonstrate that suppression of Ddx19a results in an increase of R-loops and reduced LSD1-mediated gene silencing. We further show that DDX19A binds to tri-methylated lysine 27 of histone 3 (H3K27me3) and it regulates gene expression through the removal of transcription promoting R-loops. Our results uncover a novel transcriptional regulatory cascade where the downregulation of genes is dependent on the LSD1 mediated demethylation of histone H3 lysine 4 (H3K4). This allows the polycomb repressive complex 2 (PRC2) to methylate H3K27, which serves as a binding site for DDX19A. Finally, the binding of DDX19A leads to the efficient removal of R-loops at active promoters, which further de-represses LSD1 and PRC2, establishing a positive feedback loop leading to a robust repression of the target gene.
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