Affinage

KMT5C

Histone-lysine N-methyltransferase KMT5C · UniProt Q86Y97

Length
462 aa
Mass
52.1 kDa
Annotated
2026-06-10
33 papers in source corpus 24 papers cited in narrative 24 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

KMT5C (SUV420H2) is a SAM-dependent lysine methyltransferase that deposits di- and trimethylated H4K20 (H4K20me2/3) to establish and maintain repressive heterochromatin, thereby controlling genome integrity, gene expression, differentiation, and metabolism (PMID:23599346, PMID:24396869). Structurally it carries a unique N-terminal domain and a Zn-binding post-SET domain, prefers monomethylated H4K20 as substrate, and is intrinsically limited to producing dimethyl product by a conserved serine that hydrogen-bonds the target lysine, with transition-state geometry favoring H4K20me2 over me1 or me3 (PMID:24396869, PMID:27105552, PMID:28489369). The enzyme is stably retained at pericentric heterochromatin through a heterochromatic targeting module that engages the HP1 chromoshadow domain; this module contains multiple HP1-binding motifs tethered by a length-constrained intrinsically disordered linker that confers avidity-based, cooperative HP1 locking on H3K9me3 chromatin (PMID:19486527, PMID:39562713, PMID:38403935). At heterochromatin, KMT5C-generated H4K20me3 maintains chromatin compaction, recruits cohesin to enable sister chromatid cohesion and accurate chromosome segregation, organizes 3D chromatin architecture, and represses repetitive elements (PMID:23599346, PMID:33144397). It silences specific gene promoters by antagonizing hMOF-mediated H4K16 acetylation and blocking RNA Pol II escape from promoter-proximal pausing (PMID:21321083). KMT5C acts as an epigenetic switch in cell-fate programs including myogenic and osteoblast differentiation (PMID:21206904, PMID:27862226), and controls thermogenic and gluconeogenic metabolism both catalytically — repressing Trp53 and 4e-bp1 promoters in adipocytes (PMID:32839323, PMID:38713533) — and non-catalytically, by shielding PGC-1α from RNF34-mediated ubiquitination (PMID:39929827). In cancer, loss of KMT5C-dependent H4K20me3 de-represses pro-tumorigenic loci and influences EMT, invasion, drug resistance, and immune evasion, while its methyltransferase activity additionally promotes RAD51/RAD54-mediated homologous recombination repair (PMID:36402192, PMID:37556368, PMID:40126333). Beyond canonical heterochromatin, KMT5C can deposit H4K20me3 at H3K9me3-negative loci via the partner ZNF280C, indicating an HP1-independent targeting route (PMID:42182233).

Mechanistic history

Synthesis pass · year-by-year structured walk · 23 steps
  1. 2009 High

    Established how KMT5C is anchored to heterochromatin, answering what tethers the enzyme stably to its site of action.

    Evidence TAP-MS, FRAP and domain mapping identifying HP1 binding via an 88-aa heterochromatic targeting module

    PMID:19486527

    Open questions at the time
    • Did not resolve the stoichiometry or cooperativity of HP1 engagement
    • No structural model of the HTM-HP1 interface
  2. 2010 Medium

    Connected KMT5C heterochromatin targeting to a cell-fate decision, showing it functions as an epigenetic switch in differentiation.

    Evidence Immunofluorescence, HP1α co-expression and C2C12 myogenic differentiation assays

    PMID:21206904

    Open questions at the time
    • Gain-of-function only; loss-of-function not tested here
    • Target genes driving the myogenic switch not defined
  3. 2011 High

    Defined a mechanism of gene repression, showing H4K20me3 antagonizes H4K16 acetylation to control transcription elongation.

    Evidence ChIP for multiple histone marks, siRNA, DNA-methylation inhibition and Pol II pausing assays with epistatic rescue

    PMID:21321083

    Open questions at the time
    • Mechanism by which H4K20me3 excludes hMOF not resolved
    • Generality across loci untested in this study
  4. 2013 High

    Revealed a structural role for KMT5C in mitotic chromosome biology by linking it physically and functionally to cohesin loading at heterochromatin.

    Evidence Tandem affinity purification, reciprocal Co-IP in vitro and in vivo, FRAP, and Suv4-20h KO phenotyping of cohesion and segregation

    PMID:23599346

    Open questions at the time
    • Whether cohesin recruitment requires catalytic H4K20me3 or scaffolding alone not separated
    • Direct cohesin-binding interface not mapped
  5. 2013 High

    Provided the structural and biochemical basis for KMT5C's product specificity, explaining why it stops at H4K20me2 in vitro.

    Evidence X-ray crystallography of SUV420H2-SAM and in vitro radioactivity-based methyltransferase assays

    PMID:24396869

    Open questions at the time
    • Apparent me2-only ceiling in vitro is hard to reconcile with H4K20me3 deposition in cells
    • No structure of an enzyme-nucleosome complex
  6. 2016 High

    Extended KMT5C activity beyond histones by defining its recognition motif and identifying non-histone substrates.

    Evidence In vitro methylation assays and SPOT peptide array substrate-specificity mapping

    PMID:27105552

    Open questions at the time
    • Non-histone substrate methylation not validated in cells
    • Functional consequence of CASZ1/MIS18B/CENPU methylation unknown
  7. 2016 Medium

    Established KMT5C as required for osteoblast differentiation, broadening its role across cell-lineage programs.

    Evidence siRNA knockdown with H4K20 methylation, osteogenic marker expression and mineralization assays

    PMID:27862226

    Open questions at the time
    • Direct gene targets in osteoblasts not identified
    • siRNA only; no genetic or in vivo confirmation
  8. 2017 Medium

    Provided a computational mechanistic explanation for KMT5C's dimethyl product specificity at the transition-state level.

    Evidence QM/MM molecular dynamics and free-energy (potential of mean force) simulations

    PMID:28489369

    Open questions at the time
    • No experimental mutagenesis validation of predicted catalytic determinants
    • Does not address in vivo H4K20me3
  9. 2017 Medium

    Linked KMT5C-mediated repression to cancer cell identity, showing it enforces mesenchymal state and stemness.

    Evidence siRNA knockdown with EMT-marker, stemness and drug-sensitivity profiling in pancreatic cancer lines

    PMID:29229751

    Open questions at the time
    • Specific repressed epithelial gene targets not enumerated
    • Knockdown only; no in vivo validation
  10. 2020 High

    Demonstrated genome-wide that KMT5C is the principal H4K20me3 writer controlling repeat silencing and 3D chromatin architecture.

    Evidence ESC knockout with ChIP-seq, RNA-seq and Hi-C

    PMID:33144397

    Open questions at the time
    • Causal link between compartment switching and transcriptional changes not dissected
    • Mechanism of repeat de-repression beyond H4K20me3 loss unresolved
  11. 2020 High

    Established a physiological metabolic role, showing KMT5C represses Trp53 to enable adipose thermogenesis.

    Evidence Adipocyte-specific KO mice with ChIP at the Trp53 promoter and metabolic phenotyping

    PMID:32839323

    Open questions at the time
    • How β3-adrenergic signaling induces KMT5C transcription not defined
    • Whether other adipose targets contribute not addressed
  12. 2021 Medium

    Revealed KMT5C as a target of viral subversion, where influenza NP inactivates it to release cohesin and reprogram chromatin loops.

    Evidence Co-IP of NP-Suv4-20h2, Suv4-20h2 deletion, chromatin conformation analysis and in vivo infection

    PMID:34169237

    Open questions at the time
    • Molecular basis of NP-mediated inactivation not defined
    • Single-lab finding without independent confirmation
  13. 2022 Medium

    Connected loss of KMT5C-dependent repression to targeted-therapy resistance via lncRNA-driven bypass signaling.

    Evidence KMT5C knockdown/KO, ChIP at LINC01510, LINC01510 rescue, and drug-resistance assays in NSCLC

    PMID:35404406

    Open questions at the time
    • Mechanism linking LINC01510 to MET transcription not fully resolved
    • Single-lab finding
  14. 2022 High

    Tied KMT5C-maintained heterochromatin compaction to genome stability and tumor suppression in the intestine.

    Evidence Patient-derived and mouse organoids, MNase compaction assay, ChIP, R-loop detection and xenografts

    PMID:36402192

    Open questions at the time
    • How H4K20me3 loss promotes R-loops mechanistically unclear
    • Right-sided specificity determinants not defined
  15. 2023 Medium

    Identified a catalytic role for KMT5C in DNA repair by promoting RAD51/RAD54 complex formation during homologous recombination.

    Evidence Co-IP of KMT5C-RAD51, complex-formation analysis, methyltransferase inhibitor A196, knockdown and xenografts

    PMID:37556368

    Open questions at the time
    • The relevant methylation substrate in HR not identified
    • Single Co-IP-based interaction without reciprocal structural mapping
  16. 2023 Medium

    Added a cancer-survival target gene, placing KMT5C-mediated H4K20me3 upstream of DHRS2-dependent apoptosis control.

    Evidence siRNA knockdown, ChIP at DHRS2 promoter, epistatic co-knockdown rescue and A-196 treatment in RCC

    PMID:37119764

    Open questions at the time
    • Recruitment mechanism to the DHRS2 locus unknown
    • Single-lab finding
  17. 2024 High

    Resolved the biophysical logic of heterochromatin retention, showing two HP1 modules joined by a length-constrained disordered linker confer cooperative binding.

    Evidence FRAP, domain mutagenesis and heterologous linker swaps in recruitment assays

    PMID:39562713

    Open questions at the time
    • Atomic structure of the two-module-HP1 assembly not determined
    • How retention couples to catalytic turnover unaddressed
  18. 2024 Medium

    Dissected the individual HP1-binding motifs, defining one motif as critical for locking HP1 onto H3K9me3 heterochromatin.

    Evidence Domain mapping, V374D point mutagenesis and live-cell imaging with HP1 stability assays

    PMID:38403935

    Open questions at the time
    • Functional consequence of HP1 stabilization vs destabilization for catalysis not tested
    • Single-lab finding
  19. 2024 Medium

    Extended adipose regulation, showing KMT5C-dependent repression of 4e-bp1 raises PGC1α protein and thermogenic output.

    Evidence Suv420h2 KO and adipocyte-specific overexpression mice, ChIP at the 4e-bp1 promoter and thermogenic phenotyping

    PMID:38713533

    Open questions at the time
    • Reported H4K20me3 at 4e-bp1 vs in vitro me2-only ceiling not reconciled
    • Single-lab finding
  20. 2025 High

    Established a methyltransferase-independent function, showing KMT5C scaffolds PGC-1α stability by blocking RNF34-mediated ubiquitination in liver.

    Evidence Hepatocyte-specific KO mice, Co-IP of KMT5C-RNF34-PGC-1α, ubiquitination assays and a catalytically inactive mutant

    PMID:39929827

    Open questions at the time
    • Structural basis of the KMT5C-RNF34 competition not resolved
    • Generality of non-catalytic scaffolding to other tissues untested
  21. 2025 Medium

    Linked KMT5C to tumor immune evasion via suppression of STING-IRF3/type I IFN signaling and reduced CD8+ T cell infiltration.

    Evidence KMT5C knockdown/inhibition, STING-IRF3 and cytokine assays, immune profiling and anti-PD-1 combination in vivo

    PMID:40126333

    Open questions at the time
    • Whether immune suppression is catalytic or via DNA-repair-mediated cGAS-STING attenuation not separated
    • Single-lab finding
  22. 2025 Medium

    Added a transcription-factor-directed recruitment route, with NR2C2 bringing KMT5C to the UPP1 promoter to suppress OSCC.

    Evidence KMT5C overexpression/knockdown, ChIP at UPP1, NR2C2 recruitment assays and in vitro/in vivo functional tests

    PMID:39954852

    Open questions at the time
    • Direct KMT5C-NR2C2 interaction interface not mapped
    • Single-lab finding
  23. 2026 Medium

    Challenged the H3K9me3-prerequisite model, showing KMT5C can deposit non-canonical H4K20me3 at activating-mark loci via ZNF280C, independent of HP1.

    Evidence ChIP-seq of H4K20me3/H3K9me3/activating marks, Co-IP of KMT5C-ZNF280C and RNA-seq (preprint)

    PMID:42182233

    Open questions at the time
    • Preprint, not yet peer-reviewed
    • Functional role of non-canonical H4K20me3 at active loci undefined
    • ZNF280C recruitment mechanism not resolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how KMT5C achieves H4K20 trimethylation in cells given the in vitro and computational evidence that the isolated enzyme stops at the dimethyl product.
  • No cofactor, partner, or chromatin-context determinant identified that enables H4K20me3 deposition
  • No structure of KMT5C on a nucleosome substrate
  • Discrepancy between cellular H4K20me3 ChIP and in vitro me2-only activity unexplained

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016740 transferase activity 3 GO:0140110 transcription regulator activity 3 GO:0042393 histone binding 2 GO:0140096 catalytic activity, acting on a protein 2
Localization
GO:0000228 nuclear chromosome 4 GO:0005634 nucleus 3
Pathway
R-HSA-1266738 Developmental Biology 3 R-HSA-1430728 Metabolism 3 R-HSA-4839726 Chromatin organization 3 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-1640170 Cell Cycle 1 R-HSA-73894 DNA Repair 1
Partners
CBX5NR2C2PPARGC1ARAD51RAD54RNF34ZNF280C
Complex memberships
pericentric heterochromatin

Evidence

Reading pass · 24 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2013 SUV420H2 (KMT5C) stably associates with pericentric heterochromatin through synergistic interactions with multiple HP1 molecules, mediating chromatin compaction. Cohesin subunits interact with SUV420H2 both in vitro and in vivo, and this interaction is necessary for cohesin binding to heterochromatin. SUV420H2-deficient cells display reduced sister chromatid cohesion and chromosome segregation defects during mitosis. Tandem affinity purification, Co-IP (in vivo and in vitro), FRAP, immunofluorescence, Suv4-20h mutant cell analysis Genes & development High 23599346
2009 SUV420H2 interacts with HP1 proteins (identified as main partners by TAP-MS), with the interaction mapped to the heterochromatic targeting module (HTM) of SUV420H2 and the HP1 chromoshadow domain. FRAP reveals that SUV420H2 is strongly and stably bound to pericentric heterochromatin (in contrast to highly mobile HP1), and an 88 amino-acid HTM region recapitulates both HP1 binding and stable heterochromatin association. Tandem affinity purification/mass spectrometry (TAP-MS), FRAP, immunofluorescence, domain mapping BMC cell biology High 19486527
2013 Crystal structures of human SUV420H2 (and SUV420H1) in complex with SAM were solved at high resolution. Both enzymes have a unique N-terminal domain and Zn-binding post-SET domain, and prefer monomethylated H4K20 as substrate in vitro. No H4K20 trimethylation activity was detected for either enzyme in a radioactivity-based assay, consistent with a conserved serine residue that forms a hydrogen bond with the target lysine side-chain and limits methylation level. X-ray crystallography, in vitro radioactivity-based methyltransferase assay, substrate specificity analysis FEBS letters High 24396869
2011 SUV420H2-mediated H4K20me3 antagonizes hMOF-mediated H4K16 acetylation at gene promoters, blocking RNA Polymerase II escape from promoter-proximal pausing. Combined inhibition of H4K20me3 and DNA methylation allowed hMOF re-recruitment, H4K16Ac restoration, Pol II release into elongation, and reactivation of TMS1/ASC expression. ChIP, siRNA knockdown, pharmacological inhibition of DNA methylation, Pol II pausing assays, gene expression analysis Molecular and cellular biology High 21321083
2016 By in vitro methylation studies and SPOT peptide arrays, SUV420H2 strongly favors monomethylated H4K20 as substrate and generates only dimethylated H4K20 product. SUV420H2 recognition motif is X-Kme1-(IVLMK)-(LVFI)-X-(DEV), with relaxed specificity compared to SUV420H1. Novel non-histone substrates were identified: K1423 of Zinc finger protein castor homolog 1, K215 of Protein Mis18-beta, and K308 of Centromere protein U. In vitro methylation assay, SPOT peptide array substrate specificity mapping Journal of molecular biology High 27105552
2017 QM/MM simulations demonstrated that Suv4-20h2 (KMT5C) generates dimethylated H4K20 from monomethylated substrate due to effective transition state stabilization via CH···O interactions and a cation-π interaction. The enzyme fails to catalyze monomethylation (less effective TS stabilization) and trimethylation (H4K20me2-containing reactant complex cannot adopt a reactive near-attack configuration for methyl transfer). QM/MM molecular dynamics and free energy (potential of mean force) simulations Journal of chemical theory and computation Medium 28489369
2015 Exogenous delivery of SUV420H2 into MDA-MB-231 breast cancer cells induced selective downregulation of tensin-3 (a focal adhesion protein promoting cancer cell migration), associated with enrichment of H4K20me3 immediately upstream of the tensin-3 transcription start site. Depletion of tensin-3 suppressed breast cancer cell invasiveness, connecting SUV420H2/H4K20me3 loss to upregulation of cancer-promoting genes and invasion. Exogenous gene delivery, RNA-seq, ChIP (H4K20me3), siRNA knockdown, invasion assay Experimental cell research Medium 25814362
2017 SUV420H2 (KMT5C) represses epithelial gene expression through H4K20me3, thereby favoring the mesenchymal identity in pancreatic cancer. SUV420H2 knockdown elicited mesenchymal-to-epithelial transition, decreased stemness, and increased drug sensitivity in pancreatic cancer cell lines. siRNA knockdown, gene expression profiling, functional assays (EMT markers, stemness, drug sensitivity) The Journal of cell biology Medium 29229751
2010 SUV420H2 localizes preferentially to constitutive (pericentric) heterochromatin, and co-expression with HP1α increased its targeting to pericentromeric regions. SUV420H2 facilitated an increase in pericentric H4K20me3 and maintained a Myogenin-enriched population during myogenic differentiation in C2C12 cells, acting as an epigenetic switch for myogenesis. Immunofluorescence, gain-of-function expression, C2C12 myogenic differentiation assay, HP1α co-expression PloS one Medium 21206904
2020 SUV420H2 depletion in embryonic stem (ES) cells leads to near-complete loss of H4K20me3 genome-wide, dysregulated gene expression, and delayed ES cell differentiation. SUV420H2-bound regions are enriched at repetitive DNA elements which become de-repressed upon knockout. Loss of SUV420H2 results in A/B compartment switching, perturbed chromatin insulation, and altered chromatin interactions of pericentric heterochromatin, indicating a role in 3D chromatin architecture. SUV420H2 knockout, ChIP-seq, RNA-seq, Hi-C, ChIP for H4K20me3 Development (Cambridge, England) High 33144397
2020 KMT5C expression is induced by β3-adrenergic signaling in brown and beige fat. Adipocyte-specific KMT5C knockout leads to decreased thermogenic gene expression, susceptibility to diet-induced obesity, and glucose intolerance. Mechanistically, increased Trp53 (p53) expression due to decreased H4K20me3 on its proximal promoter is responsible for the metabolic phenotypes in KMT5C KO mice. Adipocyte-specific KO mice, ChIP (H4K20me3 at Trp53 promoter), gene expression analysis, metabolic phenotyping PNAS High 32839323
2022 Loss of KMT5C in NSCLC cells drives resistance to multiple EGFR inhibitors by upregulating the long noncoding RNA LINC01510, which promotes transcription of the oncogene MET, activating a bypass signaling mechanism. KMT5C catalyzes H4K20me3 required for repression of LINC01510. KMT5C knockdown/knockout, gene expression analysis, ChIP (H4K20me3), LINC01510 overexpression rescue, in vitro and in vivo drug resistance assays Cancer research Medium 35404406
2021 Upon influenza virus infection, the viral nucleoprotein (NP) binds Suv4-20h2, inactivating it and causing dissociation of cohesin from Suv4-20h2. This inactivation allows cohesin-mediated chromatin loop formation at HoxC8-HoxC6 loci, upregulating HoxC8 and HoxC6, which enhance viral replication by inhibiting Wnt-β-catenin-mediated interferon response. Co-IP (NP-Suv4-20h2 interaction), genetic deletion of Suv4-20h2, chromatin conformation analysis, in vivo influenza infection model iScience Medium 34169237
2022 Suv4-20h2-mediated H4K20me3 is required for maintaining heterochromatin compaction in intestinal organoids and to prevent R-loop formation. Loss of Suv4-20h2 in right-sided colorectal cancer is associated with increased chromatin accessibility, stemness/Wnt signaling, and drives tumor progression; re-compaction with a histone demethylase inhibitor selectively reduced growth of right-sided cancer-derived tumors. Patient-derived organoids, mouse intestinal organoids, genetic manipulation, MNase assay, ChIP, gene expression profiling, xenograft transplantation Gastroenterology High 36402192
2023 KMT5C (SUV420H2) interacts with RAD51 and promotes RAD51/RAD54 complex formation, activating double-strand break repair by homologous recombination. This function depends on KMT5C methyltransferase activity. KMT5C knockdown or pharmacological inhibition with A196 sensitizes liver cancer cells to PARP inhibitors. Co-IP (KMT5C-RAD51), RAD51/RAD54 complex analysis, methyltransferase inhibitor (A196) treatment, KMT5C knockdown, DNA repair assays, xenograft models Hepatology Medium 37556368
2024 KMT5C heterochromatin retention is conferred by two HP1-interaction modules in the HTM, tethered by an intrinsically disordered linker. The first module uses adjacent sequences for avidity-based HP1 binding; the second increases HP1 effective concentration. FRAP reveals KMT5C undergoes rapid internal diffusion but minimal nucleoplasmic exchange. The linker is under evolutionary constraint for functional length, enabling cooperativity between modules across orthologs. FRAP, domain mutagenesis, heterologous linker experiments, heterochromatin recruitment assays EMBO reports High 39562713
2024 Three HP1-binding motifs were identified within the SUV420H2 HTM. The HTM N-terminal region (containing first and second motifs) stabilizes HP1 on heterochromatin. The HTM C-terminal region (third motif) destabilizes HP1 on chromatin. An HTM V374D mutant (Val374→Asp in the second HP1 binding motif) localizes to heterochromatin without affecting HP1 stability, demonstrating the second motif is critical for locking HP1 on H3K9me3-enriched heterochromatin. Domain mapping, point mutagenesis (V374D), live-cell fluorescence imaging, HP1 stability assays Genes to cells Medium 38403935
2025 KMT5C regulates hepatic gluconeogenesis through a non-catalytic mechanism: it impedes the E3 ligase RNF34 from binding the C-terminal of PGC-1α, thereby blocking ubiquitination-mediated PGC-1α degradation and maintaining gluconeogenic gene expression. This function is independent of KMT5C methyltransferase activity. Hepatocyte-specific KO mice, Co-IP (KMT5C-RNF34-PGC-1α), ubiquitination assay, methyltransferase-inactive mutant, gluconeogenesis and glucose output assays Nature communications High 39929827
2024 SUV420H2 (Suv420h2) catalyzes H4K20 trimethylation at the 4e-bp1 promoter, leading to downregulated expression of 4E-BP1 (a negative regulator of translation initiation), which in turn increases PGC1α protein levels and thermogenic gene expression in brown/beige adipocytes. Suv420h2 KO and adipocyte-specific overexpression mice, ChIP (H4K20me3 at 4e-bp1 promoter), gene and protein expression analysis, cold tolerance and obesity phenotyping JCI insight Medium 38713533
2025 KMT5C activates the DNA repair response and inhibits the STING-IRF3 pathway and downstream type I IFN signaling in NSCLC, reducing CCL5 secretion and CD8+ T cell infiltration, thereby facilitating tumor immune evasion. Pharmacological inhibition (A196) or genetic inhibition of KMT5C synergizes with anti-PD-1 therapy. KMT5C knockdown/inhibition, STING-IRF3 pathway assays, cytokine measurement, immune cell profiling, in vivo mouse lung cancer models with anti-PD-1 combination Advanced science Medium 40126333
2023 SUV420H2 (KMT5C) epigenetically silences DHRS2 through H4K20me3 deposition at its promoter in renal cell carcinoma. SUV420H2 knockdown leads to DHRS2 upregulation and cell apoptosis; co-knockdown of DHRS2 attenuates this effect, placing SUV420H2-mediated H4K20me3 upstream of DHRS2-dependent cell survival. siRNA knockdown, ChIP (H4K20me3 at DHRS2 promoter), rescue co-knockdown, A-196 inhibitor treatment, cell viability/apoptosis assays Biochemical and biophysical research communications Medium 37119764
2025 KMT5C suppresses OSCC progression by epigenetically silencing UPP1 via H4K20me3 deposition at the UPP1 promoter. Transcription factor NR2C2 is responsible for recruiting KMT5C to the UPP1 promoter to achieve this H4K20me3 modification and transcriptional inhibition. KMT5C overexpression and knockdown, ChIP (H4K20me3 at UPP1 promoter), NR2C2 interaction/recruitment assay, in vitro and in vivo functional assays Laboratory investigation Medium 39954852
2016 Suv420h2 loss-of-function (siRNA depletion) in osteoblast precursors results in loss of H4K20 methylation and decreased expression of osteogenic biomarkers (alkaline phosphatase/Alpl) and transcription factors (Sp7/Osterix), and impairs matrix mineralization, establishing Suv420h2 as required for normal osteoblast differentiation progression. siRNA knockdown, H4K20 methylation assay, gene expression analysis, alkaline phosphatase/mineralization assays Journal of cellular biochemistry Medium 27862226
2026 KMT5C deposits H4K20me3 in a non-canonical manner, independent of H3K9me3 (previously considered a prerequisite). This non-canonical H4K20me3 lacks canonical repressive epigenetic signatures and instead overlaps with activating marks. ZNF280C was identified as a novel KMT5C-interacting partner localizing specifically at H3K9me3-/H4K20me3+ sites, mediating HP1-independent recruitment of KMT5C to these loci. ChIP-seq (H4K20me3, H3K9me3, activating marks), biochemical pulldown/Co-IP (KMT5C-ZNF280C), RNA-seq upon KMT5C loss bioRxivpreprint Medium 42182233

Source papers

Stage 0 corpus · 33 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2006 Loss of DNA methylation and histone H4 lysine 20 trimethylation in human breast cancer cells is associated with aberrant expression of DNA methyltransferase 1, Suv4-20h2 histone methyltransferase and methyl-binding proteins. Cancer biology & therapy 107 16322686
2006 Histone H3 lysine 9 and H4 lysine 20 trimethylation and the expression of Suv4-20h2 and Suv-39h1 histone methyltransferases in hepatocarcinogenesis induced by methyl deficiency in rats. Carcinogenesis 101 16497704
2013 Suv4-20h2 mediates chromatin compaction and is important for cohesin recruitment to heterochromatin. Genes & development 100 23599346
2011 SUV420H2-mediated H4K20 trimethylation enforces RNA polymerase II promoter-proximal pausing by blocking hMOF-dependent H4K16 acetylation. Molecular and cellular biology 76 21321083
2019 miR-29a contributes to breast cancer cells epithelial-mesenchymal transition, migration, and invasion via down-regulating histone H4K20 trimethylation through directly targeting SUV420H2. Cell death & disease 71 30792382
2013 Crystal structures of the human histone H4K20 methyltransferases SUV420H1 and SUV420H2. FEBS letters 56 24396869
2022 Loss of KMT5C Promotes EGFR Inhibitor Resistance in NSCLC via LINC01510-Mediated Upregulation of MET. Cancer research 40 35404406
2017 SUV420H2 is an epigenetic regulator of epithelial/mesenchymal states in pancreatic cancer. The Journal of cell biology 38 29229751
2015 SUV420H2 suppresses breast cancer cell invasion through down regulation of the SH2 domain-containing focal adhesion protein tensin-3. Experimental cell research 38 25814362
2009 The histone methyltransferase SUV420H2 and Heterochromatin Proteins HP1 interact but show different dynamic behaviours. BMC cell biology 38 19486527
2010 Comparative analyses of SUV420H1 isoforms and SUV420H2 reveal differences in their cellular localization and effects on myogenic differentiation. PloS one 34 21206904
2016 Specificity of the SUV4-20H1 and SUV4-20H2 protein lysine methyltransferases and methylation of novel substrates. Journal of molecular biology 31 27105552
2020 KMT5c modulates adipocyte thermogenesis by regulating Trp53 expression. Proceedings of the National Academy of Sciences of the United States of America 27 32839323
2022 Loss of SUV420H2-Dependent Chromatin Compaction Drives Right-Sided Colon Cancer Progression. Gastroenterology 24 36402192
2016 Histone H4 Methyltransferase Suv420h2 Maintains Fidelity of Osteoblast Differentiation. Journal of cellular biochemistry 24 27862226
2020 H4K20me3 methyltransferase SUV420H2 shapes the chromatin landscape of pluripotent embryonic stem cells. Development (Cambridge, England) 19 33144397
2020 Circular RNA MYLK Promotes Hepatocellular Carcinoma Progression Through the miR29a/KMT5C Signaling Pathway. OncoTargets and therapy 17 32904604
2023 Histone methyltransferase KMT5C drives liver cancer progression and directs therapeutic response to PARP inhibitors. Hepatology (Baltimore, Md.) 12 37556368
2017 QM/MM Investigation of Substrate and Product Specificities of Suv4-20h2: How Does This Enzyme Generate Dimethylated H4K20 from Monomethylated Substrate? Journal of chemical theory and computation 12 28489369
2020 Loss of histone H4 lysine 20 trimethylation in osteosarcoma is associated with aberrant expression ofhistone methyltransferase SUV420H2. Oncology letters 10 32774499
2024 Impact of Histone Lysine Methyltransferase SUV4-20H2 on Cancer Onset and Progression with Therapeutic Potential. International journal of molecular sciences 7 38473745
2024 Mode of SUV420H2 heterochromatin localization through multiple HP1 binding motifs in the heterochromatic targeting module. Genes to cells : devoted to molecular & cellular mechanisms 6 38403935
2023 Epigenetic regulation of DHRS2 by SUV420H2 inhibits cell apoptosis in renal cell carcinoma. Biochemical and biophysical research communications 6 37119764
2025 Non-catalytic mechanisms of KMT5C regulating hepatic gluconeogenesis. Nature communications 5 39929827
2024 The histone methyltransferase SUV420H2 regulates brown and beige adipocyte thermogenesis. JCI insight 5 38713533
2021 Suv4-20h2 protects against influenza virus infection by suppression of chromatin loop formation. iScience 5 34169237
2020 Impact of histone methyltransferase SUV420H2 in breast cancer. Biomedical reports 4 32765868
2025 Targeting KMT5C Suppresses Lung Cancer Progression and Enhances the Efficacy of Immunotherapy. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 3 40126333
2025 Lysine Methyltransferase 5C (KMT5C) Suppresses Oral Squamous Cell Carcinoma Progression by Epigenetic Regulation of Uridine Phosphorylase 1 Expression. Laboratory investigation; a journal of technical methods and pathology 2 39954852
2026 Lysine methyltransferase 5C (KMT5C) promoted malignant growth of prostate cancer through FGFR1/STAT3 pathway and regulated the immune response. Cellular signalling 0 42134516
2026 KMT5C-H4K20me3 drives changes in epigenetic landscape independent of H3K9me3. bioRxiv : the preprint server for biology 0 42182233
2025 Insight into the mechanisms and dysregulation of KMT5C-H4K20me3 in cancer. Epigenetics 0 41108066
2024 KMT5C leverages disorder to optimize cooperation with HP1 for heterochromatin retention. EMBO reports 0 39562713

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