Affinage

KDM1A

Lysine-specific histone demethylase 1A · UniProt O60341

Length
852 aa
Mass
92.9 kDa
Annotated
2026-06-10
100 papers in source corpus 28 papers cited in narrative 28 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

KDM1A/LSD1 is a FAD-dependent histone demethylase that serves as a central, context-dependent epigenetic regulator of transcription, development, and genome maintenance (PMID:15620353). Its canonical activity removes mono- and di-methyl marks from histone H3 lysine 4 (H3K4me1/2), generating formaldehyde and repressing target genes, while in association with the androgen receptor it instead demethylates H3K9me1/2 to activate transcription, illustrating that bound partners redirect its substrate specificity (PMID:15620353, PMID:16079795). Substrate choice and activity are governed by an extensive interaction network: high-affinity binding to CoREST through the LSD1 tower domain enables nucleosomal demethylation (PMID:21142040), while assembly with the glucocorticoid receptor restrains processivity to leave H3K4me1 and licenses receptor chromatin binding (PMID:31216473), and recruitment by sequence-specific factors such as GFI1, ZNF750, and FosL1 directs repression of differentiation, immune, and ferroptosis programs (PMID:30659187, PMID:39353440, PMID:40132584). Genome-wide, KDM1A counterbalances H3K4 methylation at enhancers to keep enhancer activity and eRNA output in check (PMID:33414108), and isogenic catalytic-dead versus null comparisons show that much of its enhancer control is demethylase-independent—loss of the protein, not loss of catalysis, drives P300/CBP-mediated H3K27 acetylation and derepression (PMID:37607921). This scaffolding role extends to DNA methylation maintenance, where KDM1A stabilizes DNMT1 and UHRF1 by engaging HDAC1 and USP7, independent of its enzymatic function (PMID:19098913, PMID:39237615). Beyond chromatin, KDM1A demethylates non-histone substrates including DNMT1, HIV Tat at K51, and cytoplasmic FKBP8, and it participates directly in DNA replication origin firing and the RNF168-dependent DNA damage response (PMID:19098913, PMID:21876670, PMID:35970393, PMID:35414135, PMID:24217620). It is regulated post-translationally by EHMT2-mediated K114 methylation read by CHD1, KAT8-mediated K117 acetylation, lactylation, and JADE-2– and TRIM21–directed proteasomal degradation (PMID:26751641, PMID:35970393, PMID:40132584, PMID:29618057). Through these activities KDM1A governs embryonic and maternal-to-zygotic transitions, hematopoietic and myogenic differentiation, neuronal maturation, retroelement silencing with antitumor immunity, and serves as a therapeutic target across several cancers (PMID:21357675, PMID:26814574, PMID:26512114, PMID:28228264, PMID:25684206, PMID:29937226).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 2004 High

    Established that an amine-oxidase enzyme could remove methyl marks from histones, defining LSD1 as the first histone demethylase and a transcriptional corepressor.

    Evidence In vitro FAD-dependent demethylase assay with formaldehyde detection plus RNAi derepression of targets

    PMID:15620353

    Open questions at the time
    • Did not define how substrate specificity is directed in vivo
    • Cofactor and complex requirements for nucleosomal substrates unresolved
  2. 2005 High

    Showed that partner binding can switch LSD1's substrate from H3K4 to H3K9, converting it from a repressor to a coactivator in androgen receptor signaling.

    Evidence Co-IP, ChIP, in vitro binding, siRNA and reporter assays with AR; pargyline inhibition

    PMID:16079795

    Open questions at the time
    • Structural basis for the H3K4-to-H3K9 specificity switch not defined
    • Whether other nuclear receptors use the same mechanism unknown at the time
  3. 2008 High

    Extended LSD1 activity beyond histones, showing it demethylates and stabilizes DNMT1 to maintain global DNA methylation.

    Evidence In vitro demethylation assay, Co-IP, conditional KO in mouse ES cells, DNMT1 stability western blot

    PMID:19098913

    Open questions at the time
    • Did not separate enzymatic from scaffolding contributions to DNMT1 stability
    • Other non-histone substrates not yet surveyed
  4. 2010 High

    Defined the molecular architecture of LSD1-CoREST binding and identified tissue-specific isoforms with distinct activities, beginning to explain context-dependent function.

    Evidence ITC and truncation mapping of CoREST linker-tower interaction; reporter and siRNA analysis of neuro-specific exon E8a isoforms

    PMID:20164337 PMID:21142040

    Open questions at the time
    • Isoform substrate specificity mechanism not yet resolved
    • How CoREST binding alters catalysis on nucleosomes not fully defined
  5. 2011 High

    Demonstrated LSD1's developmental requirement for retroelement and zygotic-gene silencing and its role in demethylating a viral non-histone substrate.

    Evidence Mouse KO with ChIP-seq at MERVL/ZGA loci; mass spectrometry of Tat K51 with ChIP and chemical inhibition

    PMID:21357675 PMID:21876670

    Open questions at the time
    • Recruitment machinery to retroelements not fully mapped
    • Generality of non-histone demethylation across substrates unknown
  6. 2013 High

    Placed LSD1 in the DNA damage response, showing damage-site recruitment and a role in repair pathway choice.

    Evidence Live-cell imaging of recruitment, RNF168 Co-IP, ChIP, HR reporter and γ-irradiation sensitivity

    PMID:24217620

    Open questions at the time
    • Direct catalytic substrate at damage sites versus scaffolding role not separated
    • Link between H3K4me2 removal and ubiquitylation mechanistically incomplete
  7. 2015 High

    Resolved how a non-catalytic isoform achieves a distinct activity through a new partner and placed LSD1 in a hematopoietic fate decision.

    Evidence In vitro demethylase assays, Co-IP, ChIP-seq of LSD1+8a with SVIL; zebrafish epistasis rescue with Etv2

    PMID:25684206 PMID:26512114

    Open questions at the time
    • Structural basis of SVIL-conferred H3K9 activity unresolved
    • Mammalian relevance of the Etv2 axis not established in this work
  8. 2016 High

    Uncovered post-translational regulation of LSD1 by methylation (with a reader) and degradation, and broadened its roles to myogenesis, neurodegeneration, and the maternal-to-zygotic transition.

    Evidence Co-crystal of K114me2-CHD1, mass spectrometry, ChIP-seq; JADE-2 degradation assays; conditional/inducible and oocyte-specific KO mice with RNA-seq/bisulfite

    PMID:26751641 PMID:26814574 PMID:28228264 PMID:28993646 PMID:29618057

    Open questions at the time
    • Interplay among K114 methylation, degradation, and complex assembly not integrated
    • Causality of LSD1 mislocalization in human neurodegeneration not established
  9. 2017 High

    Established that disrupting specific LSD1 protein-protein interfaces, not just catalysis, is required for oncogenic programs.

    Evidence Co-IP, structure-guided GFI1-LSD1 interface mutagenesis, in vivo genetic ablation in medulloblastoma models

    PMID:30659187

    Open questions at the time
    • Did not define the catalytic contribution to GFI1-driven repression
    • Generalizability beyond medulloblastoma not tested here
  10. 2018 High

    Connected LSD1 loss to retroelement-driven innate immune activation, defining a route to enhance checkpoint-blockade immunotherapy.

    Evidence CRISPR/shRNA ablation, RNA-seq, immune infiltration flow cytometry, in vivo tumor models with anti-PD-1

    PMID:29937226

    Open questions at the time
    • Catalytic versus scaffolding basis of ERV derepression not dissected
    • Direct LSD1 targets driving the dsRNA response not fully mapped
  11. 2019 High

    Showed partner-dependent tuning of LSD1 processivity by the glucocorticoid receptor and placed LSD1 inhibition as a differentiation therapy in pediatric glioma.

    Evidence Reconstituted GR-complex cell-free demethylation assay and ChIP-seq; CRISPR screen and ChIP-seq in DIPG

    PMID:31216473 PMID:31631026

    Open questions at the time
    • Structural basis of GR-imposed processivity limit not defined
    • Whether DIPG effects are catalytic or scaffolding not resolved here
  12. 2020 Medium

    Revealed that LSD1 inhibition can act by destabilizing CoREST-complex members, linking pharmacology to complex integrity.

    Evidence Pharmacological inhibition, Co-IP, HMG20B degradation with proteasome rescue, RNA-seq in Merkel cell carcinoma

    PMID:33026191

    Open questions at the time
    • Single-lab, two orthogonal methods
    • Mechanism of inhibitor-induced complex disassembly not structurally defined
  13. 2021 High

    Defined LSD1 as a genome-wide enhancer rheostat that constrains H3K4 methylation and eRNA output in stem cells and neurons.

    Evidence Conditional/inducible KO in mESCs and neurons with H3K4me1/2 and H3K27ac ChIP-seq, eRNA and RNA-seq

    PMID:33414108

    Open questions at the time
    • Did not isolate catalytic from scaffolding contribution at enhancers
    • Determinants of enhancer-specific occupancy unresolved
  14. 2022 Medium

    Extended LSD1 function to cytoplasmic non-histone substrate demethylation and to direct participation in replication origin firing.

    Evidence Co-IP and in vitro FKBP8 demethylation with KAT8 K117 acetylation; replication-factor Co-IP, DNA fiber and origin-firing assays

    PMID:35414135 PMID:35970393

    Open questions at the time
    • Single-lab evidence with two orthogonal methods each
    • Direct versus indirect role in TICRR/CDC45 loading not fully resolved
  15. 2023 High

    Dissected catalytic from scaffolding function, establishing that protein presence—via suppression of P300/CBP-driven H3K27ac—rather than demethylase activity drives enhancer repression and differentiation control.

    Evidence Isogenic catalytic-dead knockin versus knockout with H3K27ac/P300 ChIP-seq, RNA-seq, differentiation assays

    PMID:37607921

    Open questions at the time
    • How LSD1 protein physically blocks P300/CBP not structurally defined
    • Loci where catalysis remains essential not enumerated
  16. 2024 High

    Consolidated the scaffolding paradigm for DNA methylation, mapped histone-acetylation crosstalk regulating catalysis, and added an immune-silencing partner.

    Evidence Catalytic-impaired knockin with HDAC1/USP7 Co-IP and bisulfite sequencing; Y391K knockin with H3K14ac crosstalk ChIP-seq; ZNF750-KDM1A co-occupancy and KO inflammatory phenotype

    PMID:38965385 PMID:39237615 PMID:39353440

    Open questions at the time
    • Physiological signals controlling H3K14ac-mediated inhibition unclear
    • Recruitment hierarchy among ZNF750, CoREST, and LSD1 not fully resolved
  17. 2025 Medium

    Showed metabolic regulation of LSD1 by lactylation that stabilizes the protein and redirects it to repress ferroptosis in drug-resistant tumors.

    Evidence Mass spectrometry of LSD1 lactylation, Co-IP (FosL1, TRIM21), ChIP-seq, viability assays, murine resistant-tumor models

    PMID:40132584

    Open questions at the time
    • Single-lab mechanistic placement
    • Lactylation site stoichiometry and direct effect on catalysis not defined

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how LSD1's many post-translational modifications, isoforms, and partner complexes are integrated to set the balance between catalytic and scaffolding functions at any given locus.
  • No unified structural model coupling modification state to complex assembly and substrate choice
  • Catalytic versus scaffolding contributions not systematically mapped genome-wide across cell types
  • Rules governing recruitment by competing sequence-specific factors unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 8 GO:0140110 transcription regulator activity 4 GO:0042393 histone binding 2 GO:0060090 molecular adaptor activity 2 GO:0016491 oxidoreductase activity 1
Localization
GO:0005634 nucleus 4 GO:0005829 cytosol 1
Pathway
R-HSA-1266738 Developmental Biology 4 R-HSA-4839726 Chromatin organization 4 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-168256 Immune System 2 R-HSA-69306 DNA Replication 1 R-HSA-73894 DNA Repair 1
Partners
ARDNMT1GFI1HDAC1NR3C1RCOR1UHRF1USP7
Complex memberships
CoREST-HDACandrogen receptor complexglucocorticoid receptor complex

Evidence

Reading pass · 28 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2004 LSD1/KDM1A functions as a histone demethylase that specifically demethylates histone H3 lysine 4 (H3K4me1/2) via a FAD-dependent oxidation reaction that generates formaldehyde; RNAi inhibition of LSD1 causes increased H3K4 methylation and derepression of target genes, establishing LSD1 as a transcriptional corepressor. In vitro demethylase assay, RNAi knockdown, formaldehyde detection Cell High 15620353
2005 LSD1/KDM1A interacts with the androgen receptor (AR) in vitro and in vivo, and in the context of AR-dependent transcription demethylates histone H3 at lysine 9 (H3K9me1/2) to relieve repressive marks and activate AR target genes; pargyline inhibits this H3K9 demethylation activity. Co-immunoprecipitation, chromatin immunoprecipitation (ChIP), in vitro binding, siRNA knockdown, reporter assays Nature High 16079795
2008 LSD1/KDM1A demethylates and stabilizes DNMT1 protein in vitro and in vivo; Set7/9 methylates DNMT1 and LSD1 reverses this methylation, thereby preventing DNMT1 proteasomal degradation and maintaining global DNA methylation levels. In vitro demethylation assay, Co-IP, conditional knockout in mouse ES cells, western blot for DNMT1 stability Nature genetics High 19098913
2010 Alternative splicing of LSD1/KDM1A generates neuro-specific isoforms (containing exon E8a) that show reduced repressor activity on reporter genes compared to ubiquitous isoforms; knockdown of neuro-specific variants inhibits neurite maturation while knockdown of ubiquitous isoforms has no morphogenic effect, indicating isoform-specific functions. Reporter gene assay, siRNA knockdown, immunofluorescence, morphometric analysis of neurite outgrowth The Journal of neuroscience Medium 20164337
2010 LSD1/KDM1A binds CoREST with high affinity (Kd ~16 nM) in a 1:1 stoichiometry; the central binding determinant is the CoREST linker region (residues 293–380) that contacts the LSD1 tower domain in a triple-helical bundle, an interaction required for demethylation of nucleosomal substrates. Isothermal titration calorimetry (ITC), structure-driven truncation analysis Biochemistry High 21142040
2011 LSD1/KDM1A represses endogenous retroviral elements (MERVL) and adjacent genes in mouse embryos and ES cells; loss of KDM1A leads to increased H3K4 methylation, increased H3K27 acetylation, and decreased H3K9 methylation at MERVL elements and flanking ZGA genes, causing embryonic arrest at gastrulation. Mouse genetic knockout, genome-wide epigenetic profiling (ChIP-seq), ES cell analysis Genes & development High 21357675
2011 LSD1/KDM1A demethylates HIV Tat at K51 (monomethylation), acting as a Tat-specific demethylase; LSD1 and its cofactor CoREST associate with the HIV promoter in vivo, and this demethylation is required for subsequent K50 acetylation and full activation of HIV transcription in latently infected T cells. Mass spectrometry on immunoprecipitated Tat, modification-specific antibodies, ChIP, shRNA knockdown, monoamine oxidase inhibitor treatment PLoS pathogens High 21876670
2013 LSD1/KDM1A is recruited directly to DNA damage sites in an RNF168-dependent manner; LSD1 demethylates H3K4me2 at damage sites, and its loss reduces histone ubiquitylation in late S/G2, impairs 53BP1 and BRCA1 complex recruitment, increases homologous recombination, and causes hypersensitivity to γ-irradiation. Live cell imaging to DNA damage sites, Co-IP (LSD1–RNF168), ChIP, siRNA knockdown, γ-H2AX foci, HR reporter assay The Journal of cell biology High 24217620
2015 The LSD1+8a neuro-specific isoform cannot intrinsically demethylate H3K4me2; instead it mediates H3K9me2 demethylation in collaboration with supervillin (SVIL), a newly identified LSD1+8a interacting protein; SVIL co-localizes at LSD1+8a-bound promoters, and SVIL knockdown mimics LSD1+8a loss (increased H3K9me2, impaired neuronal differentiation). In vitro demethylase assay, Co-IP, ChIP-seq, siRNA knockdown, histone mass spectrometry Molecular cell High 25684206
2015 LSD1/KDM1A promotes hematopoietic commitment of hemangioblasts in zebrafish by suppressing expression of Etv2, an endothelial regulator; knockdown of Etv2 rescues hematopoietic defects in lsd1 mutant embryos, placing LSD1 upstream of Etv2 in the hematopoietic fate decision. Zebrafish genetic mutant, morpholino knockdown epistasis rescue, in situ hybridization Proceedings of the National Academy of Sciences of the United States of America Medium 26512114
2016 EHMT2 dimethylates KDM1A at K114 (K114me2), and CHD1 is a reader of this mark; co-crystal structure of the KDM1A K114me2 peptide–CHD1 complex was solved; genome-wide analyses show chromatin colocalization of KDM1A K114me2, CHD1, and AR in prostate tumor cells, linking this modification to androgen-dependent transcription and TMPRSS2-ERG gene fusion. Mass spectrometry, Co-crystal structure (X-ray crystallography), ChIP-seq, Co-IP Nature structural & molecular biology High 26751641
2016 KDM1A-mediated H3K4me2 demethylation at the MyoD core enhancer is required for RNA Pol II recruitment and transcription of the non-coding enhancer RNA (CEeRNA) that drives MyoD expression; conditional LSD1 inactivation in muscle progenitors delays MyoD expression in embryonic limb buds. ChIP, siRNA knockdown in myoblasts, conditional mouse knockout, reporter assays for enhancer RNA Cell reports Medium 28228264
2016 In adult mice, inducible deletion of LSD1/KDM1A leads to paralysis and widespread hippocampal and cortical neurodegeneration with learning/memory defects; loss of LSD1 induces transcription of stem cell genes and neurodegeneration-associated pathways, and LSD1 is mislocalized to pathological protein aggregates in Alzheimer's disease and frontotemporal dementia brain tissue. Inducible conditional knockout, behavioral testing, immunofluorescence, RNA-seq, brain tissue staining from AD/FTD cases Nature communications Medium 28993646
2016 Maternally provided LSD1/KDM1A in the oocyte is required for the maternal-to-zygotic transition in mice; loss of maternal LSD1 causes embryonic arrest at the 1–2 cell stage; partial maternal loss results in altered DNA methylation and expression at imprinted genes and perinatal/behavioral phenotypes. Conditional oocyte-specific knockout in mice, bisulfite sequencing, RNA-seq, behavioral assays eLife Medium 26814574
2017 LSD1/KDM1A physically associates with GFI1 in medulloblastoma cells; GFI1 proteins engineered to be unable to recruit LSD1 cannot drive tumorigenesis; genetic ablation of LSD1 impairs tumor growth in vivo, demonstrating that the GFI1–LSD1 interaction is required for GFI1-mediated transformation and repression of neuronal differentiation genes. Co-immunoprecipitation, structure-guided mutagenesis of GFI1-LSD1 interface, mouse genetic ablation, in vivo tumor models Nature communications High 30659187
2018 LSD1 ablation in cancer cells increases endogenous retroviral element (ERV) expression and decreases RISC components, leading to dsRNA accumulation, type I interferon activation, and enhanced anti-tumor T cell immunity; this mechanism underlies sensitization to anti-PD-1 checkpoint blockade. Genetic ablation (CRISPR/shRNA), RNA-seq, flow cytometry for immune infiltration, in vivo tumor models with checkpoint blockade Cell High 29937226
2018 Glucocorticoid signaling induces expression of the ubiquitin E3 ligase JADE-2, which mediates proteasomal degradation of LSD1/KDM1A; loss of LSD1 activity during myogenic differentiation de-represses oxidative metabolism genes accompanied by increased H3K4 methylation at those loci, revealing a glucocorticoid–LSD1–metabolism axis. Western blot (proteasome inhibitors, JADE-2 siRNA), ChIP-seq, RNA-seq, metabolic assays Nucleic acids research Medium 29618057
2019 KDM1A inhibition in DIPG cells increases H3K27me3 levels at differentiation genes and simultaneously increases H3K27ac and H3K4me1, driving therapeutic differentiation; a CRISPR screen identified KDM1A knockout as sensitizing DIPG cells to HDAC inhibitors. CRISPR screen, ChIP-seq, western blot for histone marks, cell death/differentiation assays, xenograft models Cancer cell Medium 31631026
2019 KDM1A binds GR as an integral complex component; in cell-free assays GR modulates KDM1A-catalyzed H3K4 progressive demethylation by limiting removal to H3K4me2 while leaving H3K4me1; in cells KDM1A removes H3K4me2 at GR binding sites, and blocking KDM1A catalysis prevents GR chromatin binding and dysregulates GR target genes. Biochemical purification of nuclear GR complex, cell-free demethylation assay, ChIP-seq, pharmacological inhibition Cell reports High 31216473
2020 LSD1 inhibition in Merkel cell carcinoma disrupts the LSD1–CoREST complex leading to displacement and proteasomal degradation of HMG20B/BRAF35, a complex member essential for MCC proliferation; this is accompanied by derepression of neuronal lineage transcription factors. Pharmacological inhibition, Co-IP, western blot for HMG20B degradation, proteasome inhibitor rescue, RNA-seq EMBO molecular medicine Medium 33026191
2021 KDM1A maintains genome-wide optimal enhancer activity in mouse ESCs and postmitotic neurons by counterbalancing H3K4 methylation; KDM1A loss leads to increased H3K4 methylation, increased H3K27 acetylation, and elevated eRNA and target gene expression at KDM1A-occupied enhancers. Conditional/inducible KO in mESCs and neurons, ChIP-seq (H3K4me1/2, H3K27ac), eRNA measurement, RNA-seq Genome research High 33414108
2022 KDM1A interacts with and demethylates the cytoplasmic non-histone substrate FKBP8; FKBP8 demethylation enhances its ability to stabilize BCL2, promoting liver cancer cell survival; cytoplasmic KDM1A localization and stability is promoted by KAT8-mediated acetylation at lysine-117. Co-IP, in vitro demethylation assay, western blot, KAT8 overexpression/knockdown, xenograft tumor models The Journal of biological chemistry Medium 35970393
2022 LSD1/KDM1A interacts with the DNA replication machinery and is required for euchromatic origin firing; LSD1 loss causes a genome-wide switch from early to late replication; mechanistically, LSD1 facilitates loading of TICRR onto pre-replication complexes and subsequent CDC45 recruitment during origin firing. Co-IP with replication factors, DNA fiber assay, ChIP-seq, siRNA/KO, origin firing assays Signal transduction and targeted therapy Medium 35414135
2023 Catalytic inactivation of LSD1 has only mild effects on gene expression and cellular differentiation, whereas complete loss of LSD1 protein de-represses enhancers globally by increasing H3K27ac via P300/CBP; it is the gain of P300/CBP-catalyzed H3K27ac, not loss of CoREST complex from chromatin, that drives transcription derepression and differentiation defects. CRISPR catalytic-dead knockin vs. knockout, ChIP-seq (H3K27ac, P300), RNA-seq, differentiation assays Nature communications High 37607921
2024 The LSD1 Y391K mutant is insensitive to H3K14 acetylation-mediated inhibition of H3K4 demethylase activity; K562 cells with Y391K CRISPR knockin show decreased expression of genes associated with cellular adhesion and myeloid leukocyte activation, and these genes display higher H3K14ac and lower H3K4me1, demonstrating functional crosstalk between H3K14ac and H3K4 demethylation by LSD1. CRISPR knockin of engineered mutant (Y391K), ChIP-seq, RNA-seq, in vitro demethylase assay Nature chemical biology High 38965385
2024 LSD1 controls DNA methylation in mouse ESCs via a scaffolding (demethylase-independent) mechanism: LSD1 and catalytically-impaired LSD1 both stabilize UHRF1 and DNMT1 by interacting with HDAC1 and USP7, facilitating deacetylation and deubiquitination of DNMT1/UHRF1; loss of LSD1 (but not catalytic mutant) reduces DNMT1/UHRF1 levels and causes global hypomethylation. Conditional KO, catalytically-impaired knockin (LSD1MUT), Co-IP with HDAC1/USP7, bisulfite sequencing, western blot Nature communications High 39237615
2024 ZNF750 recruits KDM1A/LSD1 to silence pattern recognition receptor genes (TLR3, IFIH1/MDA5, DDX58/RIG1) in differentiated keratinocytes; loss of ZNF750 or KDM1A results in sustained PRR expression and excessive skin inflammation resembling psoriasis that can be restored by TLR3 silencing. Conditional KO in mice, ChIP (ZNF750/KDM1A co-occupancy), siRNA knockdown, inflammatory phenotype assays Immunity Medium 39353440
2025 In BRAFi/MEKi-resistant melanoma, re-accumulated lactate induces lactylation of LSD1; lactylated LSD1 interacts with FosL1, preventing LSD1 degradation by E3 ligase TRIM21 and enhancing genomic enrichment of LSD1; lactylated LSD1-FosL1 co-directs transcription to repress ferroptosis by interfering with TFRC-mediated iron uptake. Mass spectrometry identification of LSD1 lactylation, Co-IP (LSD1–FosL1, LSD1–TRIM21), ChIP-seq, cell viability assays, murine drug-resistant tumor models Developmental cell Medium 40132584

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2004 Histone demethylation mediated by the nuclear amine oxidase homolog LSD1. Cell 3349 15620353
2005 LSD1 demethylates repressive histone marks to promote androgen-receptor-dependent transcription. Nature 1421 16079795
2008 The lysine demethylase LSD1 (KDM1) is required for maintenance of global DNA methylation. Nature genetics 648 19098913
2018 LSD1 Ablation Stimulates Anti-tumor Immunity and Enables Checkpoint Blockade. Cell 556 29937226
2012 The histone demethylase KDM1A sustains the oncogenic potential of MLL-AF9 leukemia stem cells. Cancer cell 482 22464800
2018 ORY-1001, a Potent and Selective Covalent KDM1A Inhibitor, for the Treatment of Acute Leukemia. Cancer cell 262 29502954
2015 A specific LSD1/KDM1A isoform regulates neuronal differentiation through H3K9 demethylation. Molecular cell 226 25684206
2011 Endogenous retroviruses and neighboring genes are coordinately repressed by LSD1/KDM1A. Genes & development 216 21357675
2016 LSD1: biologic roles and therapeutic targeting. Epigenomics 172 27479862
2020 LSD1: more than demethylation of histone lysine residues. Experimental & molecular medicine 150 33318631
2019 Re-programing Chromatin with a Bifunctional LSD1/HDAC Inhibitor Induces Therapeutic Differentiation in DIPG. Cancer cell 148 31631026
2010 Alternative splicing of the histone demethylase LSD1/KDM1 contributes to the modulation of neurite morphogenesis in the mammalian nervous system. The Journal of neuroscience : the official journal of the Society for Neuroscience 147 20164337
2010 Structurally designed trans-2-phenylcyclopropylamine derivatives potently inhibit histone demethylase LSD1/KDM1 . Biochemistry 141 20568732
2013 The histone demethylase LSD1/KDM1A promotes the DNA damage response. The Journal of cell biology 113 24217620
2017 Advances toward LSD1 inhibitors for cancer therapy. Future medicinal chemistry 110 28722477
2018 Pharmacological Inhibition of LSD1 for Cancer Treatment. Molecules (Basel, Switzerland) 108 30518104
2012 Lysine-specific demethylase 1 (LSD1/KDM1A/AOF2/BHC110) is expressed and is an epigenetic drug target in chondrosarcoma, Ewing's sarcoma, osteosarcoma, and rhabdomyosarcoma. Human pathology 108 22245111
2020 Biological roles of LSD1 beyond its demethylase activity. Cellular and molecular life sciences : CMLS 96 32193608
2019 LSD1/KDM1A, a Gate-Keeper of Cancer Stemness and a Promising Therapeutic Target. Cancers 91 31756917
2011 Activation of HIV transcription by the viral Tat protein requires a demethylation step mediated by lysine-specific demethylase 1 (LSD1/KDM1). PLoS pathogens 84 21876670
2020 Natural products as LSD1 inhibitors for cancer therapy. Acta pharmaceutica Sinica. B 83 32837872
2017 LSD1-Mediated Epigenetic Reprogramming Drives CENPE Expression and Prostate Cancer Progression. Cancer research 83 28916652
2021 Roles of lysine-specific demethylase 1 (LSD1) in homeostasis and diseases. Journal of biomedical science 80 34082769
2016 Irreversible LSD1 Inhibitors: Application of Tranylcypromine and Its Derivatives in Cancer Treatment. Current topics in medicinal chemistry 77 26881714
2018 Germline Lysine-Specific Demethylase 1 (LSD1/KDM1A) Mutations Confer Susceptibility to Multiple Myeloma. Cancer research 73 29559475
2019 Lsd1 as a therapeutic target in Gfi1-activated medulloblastoma. Nature communications 72 30659187
2012 Targeting the PELP1-KDM1 axis as a potential therapeutic strategy for breast cancer. Breast cancer research : BCR 72 22812534
2016 Assembly of methylated KDM1A and CHD1 drives androgen receptor-dependent transcription and translocation. Nature structural & molecular biology 69 26751641
2016 Maternally provided LSD1/KDM1A enables the maternal-to-zygotic transition and prevents defects that manifest postnatally. eLife 68 26814574
2015 KDM1 histone lysine demethylases as targets for treatments of oncological and neurodegenerative disease. Epigenomics 67 26111032
2009 New roles of flavoproteins in molecular cell biology: histone demethylase LSD1 and chromatin. The FEBS journal 65 19624733
2017 LSD1 protects against hippocampal and cortical neurodegeneration. Nature communications 64 28993646
2016 Histone demethylase LSD1 controls the phenotypic plasticity of cancer cells. Cancer science 64 27375009
2016 Therapeutic opportunities in Ewing sarcoma: EWS-FLI inhibition via LSD1 targeting. Oncotarget 60 26848860
2020 LSD1 inhibition induces differentiation and cell death in Merkel cell carcinoma. EMBO molecular medicine 59 33026191
2015 KDM1 class flavin-dependent protein lysine demethylases. Biopolymers 55 25787087
2016 Design, synthesis and biological evaluation of [1,2,4]triazolo[1,5-a]pyrimidines as potent lysine specific demethylase 1 (LSD1/KDM1A) inhibitors. European journal of medicinal chemistry 54 27769034
2018 Therapeutic Targeting of KDM1A/LSD1 in Ewing Sarcoma with SP-2509 Engages the Endoplasmic Reticulum Stress Response. Molecular cancer therapeutics 52 29997151
2015 Lysine-specific demethylase (LSD1/KDM1A) and MYCN cooperatively repress tumor suppressor genes in neuroblastoma. Oncotarget 50 26062444
2013 KDM1 is a novel therapeutic target for the treatment of gliomas. Oncotarget 50 23248157
2018 KDM1A microenvironment, its oncogenic potential, and therapeutic significance. Epigenetics & chromatin 48 29921310
2021 KDM1A inactivation causes hereditary food-dependent Cushing syndrome. Genetics in medicine : official journal of the American College of Medical Genetics 47 34906447
2016 LSD1 inhibitors: a patent review (2010-2015). Expert opinion on therapeutic patents 43 27019002
2023 Lysine-specific histone demethylase 1A (KDM1A/LSD1) inhibition attenuates DNA double-strand break repair and augments the efficacy of temozolomide in glioblastoma. Neuro-oncology 42 36652263
2019 Synthesis, structure-activity relationship studies and biological characterization of new [1,2,4]triazolo[1,5-a]pyrimidine-based LSD1/KDM1A inhibitors. European journal of medicinal chemistry 42 30780087
2017 LSD1 Controls Timely MyoD Expression via MyoD Core Enhancer Transcription. Cell reports 42 28228264
2020 Leukemia Cell of Origin Influences Apoptotic Priming and Sensitivity to LSD1 Inhibition. Cancer discovery 41 32606137
2017 Epigenetic regulation of epithelial to mesenchymal transition by the Lysine-specific demethylase LSD1/KDM1A. Biochimica et biophysica acta. Gene regulatory mechanisms 41 28720390
2015 LSD1/KDM1A promotes hematopoietic commitment of hemangioblasts through downregulation of Etv2. Proceedings of the National Academy of Sciences of the United States of America 38 26512114
2024 Tanshinone IIA destabilizes SLC7A11 by regulating PIAS4-mediated SUMOylation of SLC7A11 through KDM1A, and promotes ferroptosis in breast cancer. Journal of advanced research 37 38615741
2021 LSD1: Expanding Functions in Stem Cells and Differentiation. Cells 37 34831474
2021 Superior efficacy of co-targeting GFI1/KDM1A and BRD4 against AML and post-MPN secondary AML cells. Blood cancer journal 35 34016956
2015 KDM1A triggers androgen-induced miRNA transcription via H3K4me2 demethylation and DNA oxidation. The Prostate 35 25728837
2018 The Homeotic Protein SIX3 Suppresses Carcinogenesis and Metastasis through Recruiting the LSD1/NuRD(MTA3) Complex. Theranostics 34 29463994
2018 LSD1 mediates metabolic reprogramming by glucocorticoids during myogenic differentiation. Nucleic acids research 34 29618057
2024 Targeting LSD1 in cancer: Molecular elucidation and recent advances. Cancer letters 33 38969160
2023 Demethylase-independent roles of LSD1 in regulating enhancers and cell fate transition. Nature communications 33 37607921
2016 Inhibitors of LSD1 as a potential therapy for acute myeloid leukemia. Expert opinion on investigational drugs 33 27077938
2016 LSD1 Histone Demethylase Assays and Inhibition. Methods in enzymology 33 27372757
2017 Tranylcypromine Causes Neurotoxicity and Represses BHC110/LSD1 in Human-Induced Pluripotent Stem Cell-Derived Cerebral Organoids Model. Frontiers in neurology 32 29270148
2025 Lactylation of LSD1 is an acquired epigenetic vulnerability of BRAFi/MEKi-resistant melanoma. Developmental cell 31 40132584
2023 LSD1 in drug discovery: From biological function to clinical application. Medicinal research reviews 31 38014919
2019 GR and LSD1/KDM1A-Targeted Gene Activation Requires Selective H3K4me2 Demethylation at Enhancers. Cell reports 30 31216473
2008 NF-Y substitutes H2A-H2B on active cell-cycle promoters: recruitment of CoREST-KDM1 and fine-tuning of H3 methylations. Nucleic acids research 30 18940868
2020 Capsaicin: A "hot" KDM1A/LSD1 inhibitor from peppers. Bioorganic chemistry 29 32889380
2016 The growing structural and functional complexity of the LSD1/KDM1A histone demethylase. Current opinion in structural biology 29 27470128
2017 KDM1A/LSD1 regulates the differentiation and maintenance of spermatogonia in mice. PloS one 28 28498828
2015 Decreased Expression of CoREST1 and CoREST2 Together with LSD1 and HDAC1/2 during Neuronal Differentiation. PloS one 28 26111147
2012 Integration of ERα-PELP1-HER2 signaling by LSD1 (KDM1A/AOF2) offers combinatorial therapeutic opportunities to circumventing hormone resistance in breast cancer. Breast cancer research : BCR 28 22992372
2017 LSD1 collaborates with EZH2 to regulate expression of interferon-stimulated genes. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 26 28152483
2022 Lysine-Specific Demethylase 1 (LSD1) epigenetically controls osteoblast differentiation. PloS one 25 35255108
2022 A comprehensive comparative study on LSD1 in different cancers and tumor specific LSD1 inhibitors. European journal of medicinal chemistry 25 35820351
2018 BRMS1 coordinates with LSD1 and suppresses breast cancer cell metastasis. American journal of cancer research 25 30416854
2021 KDM1A and KDM3A promote tumor growth by upregulating cell cycle-associated genes in pancreatic cancer. Experimental biology and medicine (Maywood, N.J.) 24 34171978
2015 LSD1 is Required for Hair Cell Regeneration in Zebrafish. Molecular neurobiology 24 26008620
2024 The transcription regulators ZNF750 and LSD1/KDM1A dampen inflammation on the skin's surface by silencing pattern recognition receptors. Immunity 22 39353440
2022 Dual LSD1 and HDAC6 Inhibition Induces Doxorubicin Sensitivity in Acute Myeloid Leukemia Cells. Cancers 22 36497494
2021 KDM1A maintains genome-wide homeostasis of transcriptional enhancers. Genome research 22 33414108
2022 The Role of LSD1 and LSD2 in Cancers of the Gastrointestinal System: An Update. Biomolecules 21 35327654
2022 Lysine demethylase KDM1A promotes cell growth via FKBP8-BCL2 axis in hepatocellular carcinoma. The Journal of biological chemistry 21 35970393
2013 A hypomorphic lsd1 allele results in heart development defects in mice. PloS one 21 23637775
2010 Thermodynamic characterization of the binding interaction between the histone demethylase LSD1/KDM1 and CoREST. Biochemistry 20 21142040
2024 Strategies that regulate LSD1 for novel therapeutics. Acta pharmaceutica Sinica. B 19 38572094
2023 The KDM5B and KDM1A lysine demethylases cooperate in regulating androgen receptor expression and signalling in prostate cancer. Frontiers in cell and developmental biology 19 37152294
2024 LSD1 promotes the FSH responsive follicle formation by regulating autophagy and repressing Wt1 in the granulosa cells. Science bulletin 18 38302330
2023 Pharmacological inhibition of KDM1A/LSD1 enhances estrogen receptor beta-mediated tumor suppression in ovarian cancer. Cancer letters 18 37714256
2019 LSD1 Inhibition Attenuates Tumor Growth by Disrupting PLK1 Mitotic Pathway. Molecular cancer research : MCR 18 30760542
2024 Uncoupling histone modification crosstalk by engineering lysine demethylase LSD1. Nature chemical biology 17 38965385
2024 The scaffolding function of LSD1 controls DNA methylation in mouse ESCs. Nature communications 17 39237615
2024 MSC-derived exosomal circMYO9B accelerates diabetic wound healing by promoting angiogenesis through the hnRNPU/CBL/KDM1A/VEGFA axis. Communications biology 17 39725699
2022 Biological and therapeutic role of LSD1 in Alzheimer's diseases. Frontiers in pharmacology 17 36386192
2020 The R251Q mutation of LSD1 promotes invasion and migration of luminal breast cancer cells. International journal of biological macromolecules 17 32882276
2019 Somatic deletion of KDM1A/LSD1 gene is associated to advanced colorectal cancer stages. Journal of clinical pathology 17 31471467
2023 Targeting lysine-specific demethylase 1 (KDM1A/LSD1) impairs colorectal cancer tumorigenesis by affecting cancer cells stemness, motility, and differentiation. Cell death discovery 16 37385999
2022 KDM1A/LSD1 as a promising target in various diseases treatment by regulating autophagy network. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 16 35240522
2022 LSD1 is required for euchromatic origin firing and replication timing. Signal transduction and targeted therapy 16 35414135
2022 Aberrant expression of KDM1A inhibits ferroptosis of lung cancer cells through up-regulating c-Myc. Scientific reports 16 36357457
2021 KDM1A inhibition augments the efficacy of rapamycin for the treatment of endometrial cancer. Cancer letters 16 34673129
2019 Lysine-Specific Demethylase 1 (LSD1/KDM1A) Is a Novel Target Gene of c-Myc. Biological & pharmaceutical bulletin 16 30828079
2023 Novel dual LSD1/HDAC6 inhibitor for the treatment of cancer. PloS one 15 36595522

Missed literature

Know a paper Affinage missed for KDM1A? Flag it for the maintainers and the community.

No submissions yet.