Affinage

PRDM9

Histone-lysine N-methyltransferase PRDM9 · UniProt Q9NQV7

Length
894 aa
Mass
103.4 kDa
Annotated
2026-04-28
100 papers in source corpus 37 papers cited in narrative 34 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PRDM9 is a meiosis-specific histone methyltransferase that determines the genomic positions of meiotic recombination hotspots by binding specific DNA sequences through its rapidly evolving C2H2 zinc finger array and depositing H3K4me3 and H3K36me3 on flanking nucleosomes (PMID:20044539, PMID:22028627, PMID:27362481). PRDM9 functions as a trimer in which one zinc finger array contacts DNA while the others mediate multimerization; together with the chromatin remodeler HELLS, it pioneers nucleosome-depleted regions at hotspots, and its KRAB domain recruits CXXC1, EWSR1, and meiotic cohesins (REC8, STAG3) to tether marked hotspot DNA to the chromosome axis where SPO11-dependent double-strand breaks are initiated (PMID:31308055, PMID:32001511, PMID:27932493, PMID:30853435). The dual H3K4me3/H3K36me3 signature deposited by PRDM9 recruits the reader protein ZCWPW1, which is required for proper DSB repair and synapsis, and symmetric PRDM9 binding on both homologs promotes homolog pairing, with asymmetry underlying hybrid sterility (PMID:32744506, PMID:26840484). Heterozygous loss-of-function PRDM9 variants that impair methyltransferase activity cause premature ovarian insufficiency in humans (PMID:34257419).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 2009 High

    The identity of the trans-acting factor specifying mammalian recombination hotspot locations was unknown; three simultaneous studies showed that PRDM9's zinc finger array binds the 13-mer motif enriched at hotspots, and that PRDM9 allelic variation directly controls hotspot usage, establishing PRDM9 as the long-sought hotspot determinant.

    Evidence Population genetic association of PRDM9 alleles with hotspot usage combined with in vitro DNA binding assays and Prdm9 knockout sterility in mice

    PMID:16582607 PMID:20044538 PMID:20044539 PMID:20044541

    Open questions at the time
    • Mechanism by which PRDM9 binding leads to DSB formation was unknown
    • In vivo genome-wide binding pattern of PRDM9 had not been mapped
    • Oligomeric state of PRDM9 was not determined
  2. 2011 High

    Whether zinc finger sequence alone is sufficient to reposition hotspots in vivo was unclear; transgenic mice with modified zinc fingers demonstrated that PRDM9 DNA-binding specificity directly determines both H3K4me3 deposition sites and crossover hotspot locations genome-wide.

    Evidence Transgenic mice with engineered zinc finger arrays, ChIP-seq for H3K4me3, in vitro binding assays

    PMID:22028627

    Open questions at the time
    • Whether PRDM9 has additional histone substrates beyond H3K4 was unknown
    • Structural basis of DNA recognition was unresolved
  3. 2013 High

    The catalytic mechanism of PRDM9's methyltransferase domain was structurally undefined; the crystal structure of the PR/SET domain with H3K4me2 peptide and SAH cofactor revealed the basis for progressive mono/di/trimethylation and an autoinhibitory rearrangement by pre-SET and post-SET regions.

    Evidence X-ray crystallography with in vitro methyltransferase assays

    PMID:24095733

    Open questions at the time
    • Whether PRDM9 methylates substrates other than H3K4 was not addressed
    • Structural basis for DNA binding by the zinc finger array remained unsolved
  4. 2014 High

    PRDM9 was known only as an H3K4 methyltransferase; in vitro kinetic assays and cell-based experiments demonstrated that PRDM9 trimethylates H3K36 with comparable efficiency, revealing it as a dual-specificity histone methyltransferase, while nucleosome mapping showed PRDM9 binding creates symmetric nucleosome-depleted regions at hotspot centers.

    Evidence In vitro kinetic methyltransferase assays, cell overexpression, genome-wide MNase-seq and ChIP-seq

    PMID:24604780 PMID:24634223

    Open questions at the time
    • In vivo confirmation of H3K36me3 deposition by PRDM9 at hotspots was still missing
    • Mechanism of nucleosome remodeling at hotspots was unknown
  5. 2015 High

    PRDM9's temporal window in meiosis and its oligomeric behavior were uncharacterized; imaging showed PRDM9 is restricted to pre-leptonema through early leptonema in spermatocytes, and biochemical studies demonstrated that PRDM9 allelic variants form functional heteromeric complexes that explain allelic suppression of hotspot activity.

    Evidence Immunofluorescence with meiotic stage markers, Prdm9 KO analysis, co-immunoprecipitation and methylation assays in cultured cells

    PMID:25894966 PMID:26368021

    Open questions at the time
    • Exact stoichiometry of the PRDM9 multimer was undetermined
    • How the complex is disassembled after early leptonema was unknown
  6. 2016 High

    Multiple key questions were resolved: the structural basis of allele-specific DNA recognition was revealed by a co-crystal of zinc fingers 8–11 with hotspot DNA; in vivo ChIP-seq confirmed dual H3K4me3/H3K36me3 deposition at hotspots; and genetic reconstitution demonstrated that symmetric PRDM9 binding across homologs restores fertility in otherwise sterile hybrids.

    Evidence X-ray co-crystallography of ZnF-DNA complexes, ChIP-seq in Prdm9 KO spermatocytes, zinc finger domain knockin mice with fertility and DSB assays

    PMID:26833727 PMID:26840484 PMID:27362481

    Open questions at the time
    • How PRDM9-bound chromatin is physically tethered to the chromosome axis was not established
    • The protein partners linking PRDM9 to DSB machinery were incompletely known
  7. 2016 High

    How PRDM9 connects hotspot chromatin to the chromosome axis was unknown; interaction mapping revealed that the KRAB domain directly binds CXXC1, EWSR1, EHMT2, and CDYL, and that these complexes associate with meiotic cohesins REC8 and synaptonemal complex proteins, providing a molecular bridge between hotspot loops and the axis.

    Evidence Yeast two-hybrid, in vitro binding, and co-immunoprecipitation from mouse spermatocytes

    PMID:27932493

    Open questions at the time
    • Whether the KRAB domain is essential in vivo was not yet tested
    • The role of EWSR1 in the complex had not been functionally dissected
  8. 2017 High

    The essential role of the KRAB domain in vivo and key biophysical properties were established: KRAB truncation causes meiotic arrest; CXXC1 links PRDM9 to IHO1 (a DSB machinery component); PRDM9 automethylates post-SET lysines; allele C co-crystal reveals structural adaptations for longer recognition sequences; and DNA binding kinetics show nanomolar affinity with hours-long residence times.

    Evidence KRAB truncation knockin mice, yeast two-hybrid, co-crystallography, switchSENSE biophysics, mass spectrometry of automethylation

    PMID:28126738 PMID:28155083 PMID:28527011 PMID:28801461

    Open questions at the time
    • Whether automethylation regulates PRDM9 activity in vivo was unknown
    • The functional consequence of non-canonical PRDM9 binding sites was unclear
  9. 2018 High

    Whether methyltransferase activity is truly required for DSB formation at PRDM9 sites was formally tested: catalytically dead PRDM9 knockin mice lose both histone marks and DSBs at bound sites, proving that enzymatic activity—not just DNA binding—is essential for hotspot activation.

    Evidence Methyltransferase-dead PRDM9 knockin mice, ChIP-seq, DSB mapping

    PMID:29478809

    Open questions at the time
    • How the dual mark is read by downstream effectors was unresolved
    • Whether any non-histone substrates are biologically relevant was unknown
  10. 2019 High

    The stoichiometry of PRDM9 multimers and the cooperation between PRDM9 and meiotic cohesins were clarified: PRDM9 forms trimers mediated by zinc finger–zinc finger interactions with only one subunit contacting DNA, and PRDM9 cooperates with cohesin subunit STAG3 to promote normal DSB levels at hotspots.

    Evidence EMSA, mass spectrometry, fluorescence correlation spectroscopy for stoichiometry; co-IP and double-mutant mouse phenotyping for STAG3 interaction

    PMID:30853435 PMID:31308055

    Open questions at the time
    • How trimeric architecture influences hotspot selection or symmetric binding across homologs was unknown
    • Whether REC8 phosphorylation state regulates the PRDM9-cohesin interaction was untested
  11. 2020 High

    The chromatin remodeling and downstream reader steps were identified: HELLS forms a pioneer complex with PRDM9 required for chromatin opening at hotspots; ZCWPW1 reads the dual H3K4me3/H3K36me3 mark and is required for DSB repair and synapsis; EWSR1 bridges PRDM9 to phospho-REC8 and is essential for full histone methylation and crossover formation; and PRDM9 asymmetrically blocks MRE11 processing of SPO11 intermediates.

    Evidence Proteomic PRDM9 partner identification, Hells/Ewsr1/Zcwpw1 conditional/constitutive knockouts, ChIP-seq, ATAC-seq, END-seq in mouse spermatocytes

    PMID:32001511 PMID:32051414 PMID:32744506 PMID:33047671 PMID:33175657

    Open questions at the time
    • How HELLS is specifically recruited by PRDM9 (direct vs. indirect binding) was not fully resolved
    • Whether ZCWPW1 acts catalytically or as a scaffold at repair sites was unknown
    • The relative contributions of H3K4me3 vs. H3K36me3 to each downstream step were not separated
  12. 2021 Medium

    Whether PRDM9 haploinsufficiency causes human disease was uncertain; exome sequencing identified heterozygous PRDM9 variants in premature ovarian insufficiency patients, and in vitro assays confirmed impaired methyltransferase activity, establishing dosage-dependent PRDM9 requirement in female meiosis.

    Evidence Exome sequencing of patient cohort with in vitro methyltransferase activity validation

    PMID:34257419

    Open questions at the time
    • Sample size was limited; replication in larger cohorts is needed
    • Whether these variants affect DSB positioning or synapsis in oocytes was not examined
  13. 2023 Medium

    Additional interaction partners and non-histone substrates were identified: FUS/TLS interacts with PRDM9, colocalizes on the axis, and also contacts REC114 and SPO11; CTNNBL1 was identified as a non-histone PRDM9 methylation substrate through peptide library screening.

    Evidence Co-immunoprecipitation, ChIP-seq, peptide library screen, in vitro methyltransferase assay

    PMID:36967403 PMID:36972790

    Open questions at the time
    • Functional significance of CTNNBL1 methylation in meiosis is untested
    • FUS interaction was shown by a single lab without genetic validation
    • Whether non-histone methylation contributes to hotspot biology is unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include how the PRDM9 trimer coordinates symmetric binding across homologs, what triggers PRDM9 degradation after early leptonema, whether automethylation or non-histone substrate methylation regulates PRDM9 function in vivo, and how the pioneer complex (PRDM9–HELLS) selects individual hotspots from the larger set of potential binding sites.
  • No structural model of full-length trimeric PRDM9 on chromatin
  • Mechanism of PRDM9 turnover is unknown
  • Quantitative model linking binding affinity, chromatin state, and DSB probability is lacking

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016740 transferase activity 9 GO:0003677 DNA binding 6 GO:0042393 histone binding 3
Localization
GO:0005694 chromosome 3 GO:0005634 nucleus 2
Pathway
R-HSA-4839726 Chromatin organization 5 R-HSA-1474165 Reproduction 4 R-HSA-73894 DNA Repair 3
Partners
CXXC1EWSR1FUSHELLSIHO1REC8STAG3ZCWPW1
Complex memberships
PRDM9–CXXC1–EWSR1 axis-tethering complexPRDM9–HELLS pioneer complex

Evidence

Reading pass · 34 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2009 PRDM9 zinc finger array binds specific DNA sequence motifs (13-mer) at meiotic recombination hotspots, targeting initiation of recombination to specific genomic locations; in vitro DNA binding studies confirmed sequence-specific recognition by the human PRDM9 consensus allele. In vitro DNA binding assay, population genetic association of PRDM9 allelic variants with hotspot usage Science High 20044538 20044539 20044541
2009 PRDM9 (Meisetz) encodes a histone H3 lysine 4 trimethylase expressed in early meiosis; its deficiency results in sterility in both sexes of mice, establishing PRDM9 as required for meiotic progression. Gene knockout in mice with fertility and meiotic phenotype readout Science High 16582607 20044538
2011 PRDM9 zinc finger DNA binding specificity directly determines the genomic location of H3K4me3 marks and crossover hotspots; mutations in the zinc finger array shift hotspot activity and H3K4me3 distribution; in vitro binding of PRDM9 variants correlates with in vivo hotspot activity, and cis mutations at hotspot centers that reduce activity also reduce PRDM9 binding. Transgenic mice with modified zinc fingers, ChIP-seq for H3K4me3, in vitro DNA binding assay PLoS biology High 22028627
2013 Crystal structure of the PRDM9 methyltransferase domain in complex with H3K4me2 peptide and S-adenosylhomocysteine reveals the structural basis for H3K4 mono-, di-, and trimethylation activity; a rearrangement by pre-SET and post-SET domains creates an autoinhibited state, defining the regulatory mechanism. X-ray crystallography, in vitro methyltransferase assay Cell reports High 24095733
2014 PRDM9 trimethylates histone H3K36 in addition to H3K4 in vitro with comparable efficiency; overexpression in HEK293 cells increases both H3K4me3 and H3K36me3, confirming dual methyltransferase activity. In vitro kinetic methyltransferase assay, cell overexpression with western blot Journal of Biological Chemistry High 24634223
2016 PRDM9 trimethylates both H3K4 and H3K36 in vivo in mouse spermatocytes at recombination hotspots; H3K4me3 and H3K36me3 are correlated at hotspots, can occur on the same nucleosomes, and are dramatically reduced when PRDM9 is absent, confirming that both marks are PRDM9-dependent in meiosis. ChIP-seq in mouse spermatocytes; Prdm9 knockout comparison; in vitro dual-methylation assay PLoS genetics High 27362481
2014 PRDM9 binding actively reorganizes nucleosomes into a symmetrical, nucleosome-depleted pattern centered on the PRDM9 binding motif; DSBs are centered over this motif; H3K4me3 marks restrict the region of Holliday junction migration. Genome-wide nucleosome mapping (MNase-seq), ChIP-seq, in vitro binding, genetic cross analysis Genome research High 24604780
2016 PRDM9 KRAB domain interacts directly with CXXC1, EWSR1, EHMT2, and CDYL (confirmed by yeast two-hybrid, in vitro binding, and co-immunoprecipitation from mouse spermatocytes); PRDM9-bound complexes also associate with meiotic cohesin REC8 and synaptonemal complex proteins SYCP3/SYCP1, providing a mechanism by which hotspot DNA is brought to the chromosomal axis. Yeast two-hybrid, in vitro binding, co-immunoprecipitation from mouse spermatocytes Molecular biology of the cell High 27932493
2017 The PRDM9 KRAB domain is required for meiosis in vivo; truncation of KRAB leads to meiotic arrest and loss of PRDM9 function. CXXC1 interacts with the KRAB domain and also with IHO1 (a meiotic DSB machinery component), providing a molecular link between PRDM9-marked hotspots and the DSB initiation machinery conserved from yeast Spp1. Mouse KRAB truncation knockin, yeast two-hybrid, co-immunoprecipitation Chromosoma High 28527011
2018 PRDM9 methyltransferase activity is required for H3K4me3 and H3K36me3 deposition and for DSB formation at PRDM9-binding sites; each PRDM9 variant independently generates its own set of H3K4me3 marks, and an excess of designated sites are selected from which a subset undergoes DSB formation. Methyltransferase-dead PRDM9 knockin mice, ChIP-seq, DSB mapping Molecular cell High 29478809
2016 Re-engineering the PRDM9 DNA-binding zinc finger domain (humanizing it in C57BL/6 mice) repositions DSB hotspots and completely restores fertility in male hybrids; the degree to which PRDM9 binds both homologs symmetrically at DSB sites correlates with fertility measures, establishing that symmetric PRDM9 binding is mechanistically important for successful meiotic recombination. Zinc finger domain knockin in mice, DSB hotspot mapping, fertility assays Nature High 26840484
2015 PRDM9 nuclear localization in male germ cells is restricted to pre-leptonema through early leptonema and is no longer detectable by late zygonema; PRDM9-dependent H3K4me3 marks disappear by pachytene. Germ cells lacking PRDM9 show inefficient homology recognition, failed synapsis, and aberrant DSB repair, establishing the developmental window of PRDM9 function. Immunofluorescence with stage-specific markers, PRDM9 KO mouse analysis Chromosoma High 25894966
2020 HELLS (a SNF2-like chromatin remodeler) is recruited to hotspots by PRDM9 and is required for PRDM9 binding, histone modifications, and DNA accessibility at hotspots; in male mice lacking HELLS, DSBs are retargeted away from PRDM9-bound hotspots, causing germ cell death and sterility. HELLS and PRDM9 form a pioneer complex to open chromatin at hotspots. Proteomic identification of PRDM9 partners, Hells conditional knockout, ChIP-seq, ATAC-seq Genes & development High 32001511 33047671
2020 PRDM9 asymmetrically blocks MRE11 from releasing SPO11 from DSB intermediates; PRDM9-bound chromatin creates a SPO11-bound recombination intermediate (SPO11-RI) present at all hotspots. ATM cooperates with PRDM9 as a local regulator of SPO11 processing. END-seq on mouse spermatocytes, enzymatic modifications to END-seq, Atm-/- mouse analysis Nature communications High 32051414
2016 Crystal structure of human PRDM9 allele A zinc fingers 8-11 bound to a hotspot DNA oligonucleotide reveals that each zinc finger helix occupies the major groove and makes hydrogen bond contacts with up to four adjacent bases, predominantly purines on the complementary strand; different alleles (C, L13, L9/L24, L20) show distinct affinities and sequence preferences explainable by the structure. X-ray co-crystallography, in vitro DNA binding affinity assays for multiple alleles Genes & development High 26833727
2017 Crystal structure of PRDM9 allele C zinc fingers 8-13 bound to a C-specific hotspot DNA reveals three structural differences from allele A: Ser764 in ZF9 accommodates a variable base (vs. Arg764 recognizing guanine in allele A); a two-finger expansion allows recognition of a 3-bp-longer sequence; and an Arg-Asp dipeptide switch permits adaptability to C:G and G:C base pairs by identical ZF modules. X-ray co-crystallography Journal of Biological Chemistry High 28801461
2015 PRDM9 variants form functional heteromeric (multimeric) complexes in cell culture; when a heteromeric complex binds a hotspot, the PRDM9 variant that would not otherwise bind can still methylate nearby nucleosomes. This multimerization underlies allelic suppression of hotspots in heterozygous individuals. Co-immunoprecipitation from cell culture, in vitro binding assays, histone methylation assays PLoS genetics High 26368021
2017 In addition to canonical DNA-binding sites, PRDM9 binds in vivo to noncanonical sites lacking the consensus motif, including gene promoters (in a DSB-dependent manner) and CTCF binding sites (in a DSB-independent manner), suggesting PRDM9 interactions with genomic sequences on the chromosome axis. ChIP-seq of PRDM9 in mouse spermatocytes, comparison with SPO11-KO and PRDM9-KO controls Genome research High 28336543
2017 Human PRDM9 zinc fingers mediate protein multimerization in addition to DNA binding; PRDM9 preferentially forms homo-multimers even between highly diverged alleles. Co-immunoprecipitation in human cell line, biochemical binding assays eLife Medium 29072575
2019 PRDM9 forms a trimer (not a dimer or higher-order oligomer); the variable zinc finger array is sufficient for trimerization; only one ZnF array within the trimer contacts DNA while the remaining two maintain the trimer through ZnF-ZnF interactions. EMSA, mass spectrometry, fluorescence correlation spectroscopy with tagged PRDM9 proteins Life science alliance High 31308055
2017 The PRDM9 zinc finger domain forms a highly stable, long-lived complex with its DNA recognition sequence (dissociation half-time of many hours; KD in nanomolar range); polymorphisms in the recognition sequence directly affect binding affinity; longer targets are preferred; alternative sequences can be bound by subsets of the ZnF array. Gel mobility shift assay, switchSENSE real-time biophysical binding kinetics Chromosome research High 28155083
2019 PRDM9 interacts with meiotic cohesin subunits STAG3 and REC8; PRDM9 and STAG3 cooperatively promote normal levels of meiotic DSBs at hotspots in spermatocytes; this cooperation depends on PRDM9 methyltransferase activity; STAG3 also promotes axis localization of DSB-promoting proteins HORMAD1, IHO1, MEI4, and SPO11. Co-immunoprecipitation, genetic interaction analysis, double-mutant mouse phenotyping Current biology High 30853435
2020 EWSR1 binds both PRDM9 and phosphorylated REC8 (pREC8) in male meiotic cells; conditional knockout of Ewsr1 before meiosis causes decreased histone trimethylation at hotspots, impaired DSB repair, and reduced crossover number, establishing EWSR1 as essential for PRDM9-dependent histone methylation and as a linker between PRDM9-bound hotspots and the chromosome axis. Co-immunoprecipitation, Ewsr1 conditional knockout mouse, ChIP-seq, crossover analysis Molecular biology of the cell High 33175657
2020 ZCWPW1, containing H3K4me3 and H3K36me3 recognition domains, is strongly and specifically recruited to PRDM9 binding sites (dual-mark sites) in human cells with higher affinity than H3K4me3-alone sites; ZCWPW1 localizes to DMC1-labelled hotspots in a largely PRDM9-dependent manner; male Zcwpw1 knockout mice have normal DSB positioning but persistent DMC1 foci and severe DSB repair and synapsis defects. ChIP-seq in human cells and mouse spermatocytes, Zcwpw1 knockout mice, immunofluorescence eLife High 32374261 32744506
2019 MRK-740 is a potent, selective PRDM9 inhibitor (IC50 ~80 nM) that binds in the substrate-binding pocket with SAM-dependent substrate-competitive inhibition; in cells it specifically inhibits H3K4 methylation at endogenous PRDM9 target loci, confirming the enzymatic mechanism. Biochemical inhibition assay, structural binding characterization, cell-based H3K4me3 ChIP Nature communications High 31848333
2017 PRDM9 performs intramolecular automethylation on multiple lysine residues in the lysine-rich post-SET domain; automethylation is abolished by the C321P active-site mutation that also disrupts SAM binding. In vitro methyltransferase assay, active-site mutagenesis, mass spectrometry Biochemical Journal High 28126738
2015 QM/MM simulations of PRDM9 methyltransferase catalysis show that Y276F mutation decreases catalytic activity of H3K4me2→H3K4me3 methyl transfer (Tyr276 makes essential hydrogen bond interactions), while Y357F does not affect the methyl transfer rate, defining distinct roles for these two active-site tyrosines. QM/MM molecular dynamics and free energy simulations Journal of molecular modeling Low 25903303
2014 A C321P mutation in the PRDM9 PR/SET domain significantly weakens methyltransferase activity; recombinant PRDM9 can methylate histone octamers; comprehensive in vitro characterization identified new histone substrates. In vitro methyltransferase assay with recombinant histone octamer, site-directed mutagenesis Biochemical Journal Medium 24785241
2023 PRDM9 preferentially methylates peptide sequences not found in histones; CTNNBL1 was identified as a nonhistone substrate methylated by PRDM9 both in vitro and in cells, using peptide library screening, peptide spot arrays, and in vitro KMT assays. Lysine-oriented peptide library screen, in vitro KMT assay on recombinant proteins, cell-based methylation Journal of Biological Chemistry Medium 36972790
2023 FUS/TLS physically interacts with PRDM9 (co-immunoprecipitation in vitro and in vivo), colocalizes with PRDM9 on meiotic chromosome axes, and is recruited to H3K4me3-marked hotspots by ChIP; FUS/TLS also interacts with REC114 and SPO11, suggesting it is a component of the protein complex promoting meiotic recombination initiation. Co-immunoprecipitation, ChIP-seq, immunofluorescence Cellular and molecular life sciences Medium 36967403
2023 PRDM9 promotes H3K4me3 at the IGFBP5 promoter in periodontal ligament stem cells (a somatic context), and its depletion increases IGFBP5 transcription, cell proliferation (via downregulation of p21/p27 and upregulation of cyclin E), and cell migration. shRNA knockdown, ChIP assay for H3K4me3, microarray, flow cytometry, cell proliferation/migration assays Connective tissue research Low 31096797
2023 Glutamine induces PRDM9 expression in brown adipocytes via C/EBPβ recruitment to the PRDM9 enhancer; PRDM9 inactivation (shRNA or inhibitor) attenuates glutamine-triggered adipogenic and thermogenic gene induction, establishing a role for PRDM9-mediated H3K4me3 in thermogenic adipocyte differentiation. shRNA knockdown, chemical inhibitor, ChIP-seq, gene expression analysis in mouse adipocytes Diabetes Low 37579296
2021 Pathogenic heterozygous PRDM9 variants identified in premature ovarian insufficiency patients impair PRDM9 methyltransferase activity in functional studies, establishing a dosage-dependent requirement for PRDM9 methyltransferase activity in female meiosis. Exome sequencing plus in vitro methyltransferase activity assay for variant validation Genetics in medicine Medium 34257419
2020 PRDM9 activity depends on HELLS for its binding to hotspot DNA and is associated with enrichment of 5-hydroxymethylcytosine (5hmC) at PRDM9-binding sites; 5hmC enrichment is triggered by PRDM9 binding and histone modification but is independent of SPO11-catalyzed DSB formation. Proteomic PRDM9 partner identification, HELLS conditional KO, ChIP-seq, 5hmC mapping, SPO11-KO and methyltransferase-dead PRDM9 comparisons eLife High 33047671

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2009 PRDM9 is a major determinant of meiotic recombination hotspots in humans and mice. Science (New York, N.Y.) 765 20044539
2009 Drive against hotspot motifs in primates implicates the PRDM9 gene in meiotic recombination. Science (New York, N.Y.) 517 20044541
2009 Prdm9 controls activation of mammalian recombination hotspots. Science (New York, N.Y.) 454 20044538
2009 Accelerated evolution of the Prdm9 speciation gene across diverse metazoan taxa. PLoS genetics 229 19997497
2016 Re-engineering the zinc fingers of PRDM9 reverses hybrid sterility in mice. Nature 152 26840484
2011 Mouse PRDM9 DNA-binding specificity determines sites of histone H3 lysine 4 trimethylation for initiation of meiotic recombination. PLoS biology 136 22028627
2016 The Meiotic Recombination Activator PRDM9 Trimethylates Both H3K36 and H3K4 at Recombination Hotspots In Vivo. PLoS genetics 135 27362481
2018 PRDM9 and Its Role in Genetic Recombination. Trends in genetics : TIG 109 29366606
2011 Variants of the protein PRDM9 differentially regulate a set of human meiotic recombination hotspots highly active in African populations. Proceedings of the National Academy of Sciences of the United States of America 108 21750151
2011 Death of PRDM9 coincides with stabilization of the recombination landscape in the dog genome. Genome research 107 22006216
2015 PRDM9 drives evolutionary erosion of hotspots in Mus musculus through haplotype-specific initiation of meiotic recombination. PLoS genetics 105 25568937
2014 PRDM9 binding organizes hotspot nucleosomes and limits Holliday junction migration. Genome research 105 24604780
2020 ATM and PRDM9 regulate SPO11-bound recombination intermediates during meiosis. Nature communications 95 32051414
2014 Trimethylation of histone H3 lysine 36 by human methyltransferase PRDM9 protein. The Journal of biological chemistry 94 24634223
2018 PRDM9 Methyltransferase Activity Is Essential for Meiotic DNA Double-Strand Break Formation at Its Binding Sites. Molecular cell 92 29478809
2013 Molecular basis for the regulation of the H3K4 methyltransferase activity of PRDM9. Cell reports 90 24095733
2018 PRDM9, a driver of the genetic map. PLoS genetics 85 30161134
2017 A map of human PRDM9 binding provides evidence for novel behaviors of PRDM9 and other zinc-finger proteins in meiosis. eLife 79 29072575
2016 PRDM9 interactions with other proteins provide a link between recombination hotspots and the chromosomal axis in meiosis. Molecular biology of the cell 74 27932493
2017 The PRDM9 KRAB domain is required for meiosis and involved in protein interactions. Chromosoma 66 28527011
2009 Extraordinary molecular evolution in the PRDM9 fertility gene. PloS one 66 20041164
2011 What are the genomic drivers of the rapid evolution of PRDM9? Trends in genetics : TIG 65 21388701
2013 DNA binding specificities of the long zinc-finger recombination protein PRDM9. Genome biology 64 23618393
2014 Primate evolution of the recombination regulator PRDM9. Nature communications 62 25001002
2011 The case of the fickle fingers: how the PRDM9 zinc finger protein specifies meiotic recombination hotspots in humans. PLoS biology 61 22162947
2015 Affinity-seq detects genome-wide PRDM9 binding sites and reveals the impact of prior chromatin modifications on mammalian recombination hotspot usage. Epigenetics & chromatin 60 26351520
2012 Interallelic and intergenic incompatibilities of the Prdm9 (Hst1) gene in mouse hybrid sterility. PLoS genetics 58 23133405
2014 Diversity of Prdm9 zinc finger array in wild mice unravels new facets of the evolutionary turnover of this coding minisatellite. PloS one 56 24454780
2011 Prdm9, a major determinant of meiotic recombination hotspots, is not functional in dogs and their wild relatives, wolves and coyotes. PloS one 53 22102853
2015 Nuclear localization of PRDM9 and its role in meiotic chromatin modifications and homologous synapsis. Chromosoma 52 25894966
2020 HELLS and PRDM9 form a pioneer complex to open chromatin at meiotic recombination hot spots. Genes & development 51 32001511
2017 In vivo binding of PRDM9 reveals interactions with noncanonical genomic sites. Genome research 51 28336543
2014 Prdm9 polymorphism unveils mouse evolutionary tracks. DNA research : an international journal for rapid publication of reports on genes and genomes 50 24449848
2016 Structural basis for human PRDM9 action at recombination hot spots. Genes & development 48 26833727
2018 Modulation of Prdm9-controlled meiotic chromosome asynapsis overrides hybrid sterility in mice. eLife 46 29537370
2020 Snake Recombination Landscapes Are Concentrated in Functional Regions despite PRDM9. Molecular biology and evolution 42 31926008
2020 The histone modification reader ZCWPW1 links histone methylation to PRDM9-induced double-strand break repair. eLife 42 32374261
2015 Multimer Formation Explains Allelic Suppression of PRDM9 Recombination Hotspots. PLoS genetics 42 26368021
2014 Genetic recombination variation in wild Robertsonian mice: on the role of chromosomal fusions and Prdm9 allelic background. Proceedings. Biological sciences 42 24850922
2012 Rare allelic forms of PRDM9 associated with childhood leukemogenesis. Genome research 41 23222848
2012 Recombination regulator PRDM9 influences the instability of its own coding sequence in humans. Proceedings of the National Academy of Sciences of the United States of America 41 23267059
2009 Single-nucleotide polymorphisms of the PRDM9 (MEISETZ) gene in patients with nonobstructive azoospermia. Journal of andrology 39 19168450
2020 ZCWPW1 is recruited to recombination hotspots by PRDM9 and is essential for meiotic double strand break repair. eLife 37 32744506
2006 Meisetz, a novel histone tri-methyltransferase, regulates meiosis-specific epigenesis. Cell cycle (Georgetown, Tex.) 37 16582607
2021 Hybrid sterility genes in mice (Mus musculus): a peculiar case of PRDM9 incompatibility. Trends in genetics : TIG 34 34238593
2014 Prdm9 incompatibility controls oligospermia and delayed fertility but no selfish transmission in mouse intersubspecific hybrids. PloS one 34 24756080
2022 PRDM9 losses in vertebrates are coupled to those of paralogs ZCWPW1 and ZCWPW2. Proceedings of the National Academy of Sciences of the United States of America 33 35217607
2019 Histone methyltransferase PRDM9 is not essential for meiosis in male mice. Genome research 32 31186301
2018 Aberrant PRDM9 expression impacts the pan-cancer genomic landscape. Genome research 31 30341163
2019 Prdm9 and Meiotic Cohesin Proteins Cooperatively Promote DNA Double-Strand Break Formation in Mammalian Spermatocytes. Current biology : CB 30 30853435
2019 Discovery of a chemical probe for PRDM9. Nature communications 30 31848333
2012 High diversity at PRDM9 in chimpanzees and bonobos. PloS one 30 22768294
2008 Two single nucleotide polymorphisms in PRDM9 (MEISETZ) gene may be a genetic risk factor for Japanese patients with azoospermia by meiotic arrest. Journal of assisted reproduction and genetics 30 18941885
2024 Patterns of recombination in snakes reveal a tug-of-war between PRDM9 and promoter-like features. Science (New York, N.Y.) 28 38386752
2014 Characterization of the histone methyltransferase PRDM9 using biochemical, biophysical and chemical biology techniques. The Biochemical journal 27 24785241
2013 Characterization of Prdm9 in equids and sterility in mules. PloS one 26 23613924
2021 Rat PRDM9 shapes recombination landscapes, duration of meiosis, gametogenesis, and age of fertility. BMC biology 23 33910563
2020 Prdm9 Intersubspecific Interactions in Hybrid Male Sterility of House Mouse. Molecular biology and evolution 23 32642764
2020 PRDM9 activity depends on HELLS and promotes local 5-hydroxymethylcytosine enrichment. eLife 23 33047671
2021 Pathogenic variants of meiotic double strand break (DSB) formation genes PRDM9 and ANKRD31 in premature ovarian insufficiency. Genetics in medicine : official journal of the American College of Medical Genetics 22 34257419
2021 Cataloging Human PRDM9 Allelic Variation Using Long-Read Sequencing Reveals PRDM9 Population Specificity and Two Distinct Groupings of Related Alleles. Frontiers in cell and developmental biology 21 34805134
2019 Genomic Structure of Hstx2 Modifier of Prdm9-Dependent Hybrid Male Sterility in Mice. Genetics 21 31562180
2023 Glutamine Production by Glul Promotes Thermogenic Adipocyte Differentiation Through Prdm9-Mediated H3K4me3 and Transcriptional Reprogramming. Diabetes 18 37579296
2018 Interrogating the Functions of PRDM9 Domains in Meiosis. Genetics 18 29674518
2019 PRDM9 Diversity at Fine Geographical Scale Reveals Contrasting Evolutionary Patterns and Functional Constraints in Natural Populations of House Mice. Molecular biology and evolution 17 31004162
2017 Structural basis of human PR/SET domain 9 (PRDM9) allele C-specific recognition of its cognate DNA sequence. The Journal of biological chemistry 17 28801461
2016 Evolutionary dynamics of meiotic recombination hotspots regulator PRDM9 in bovids. Molecular genetics and genomics : MGG 17 27744561
2024 High prevalence of PRDM9-independent recombination hotspots in placental mammals. Proceedings of the National Academy of Sciences of the United States of America 16 38809707
2020 Sexual dimorphism in the meiotic requirement for PRDM9: A mammalian evolutionary safeguard. Science advances 16 33097538
2020 EWSR1 affects PRDM9-dependent histone 3 methylation and provides a link between recombination hotspots and the chromosome axis protein REC8. Molecular biology of the cell 15 33175657
2018 Construction of PRDM9 allele-specific recombination maps in cattle using large-scale pedigree analysis and genome-wide single sperm genomics. DNA research : an international journal for rapid publication of reports on genes and genomes 15 29186399
2018 Cisplatin-induced DNA double-strand breaks promote meiotic chromosome synapsis in PRDM9-controlled mouse hybrid sterility. eLife 14 30592461
2017 The long zinc finger domain of PRDM9 forms a highly stable and long-lived complex with its DNA recognition sequence. Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology 14 28155083
2024 Multiple Genomic Landscapes of Recombination and Genomic Divergence in Wild Populations of House Mice-The Role of Chromosomal Fusions and Prdm9. Molecular biology and evolution 13 38513632
2021 Altering the Binding Properties of PRDM9 Partially Restores Fertility across the Species Boundary. Molecular biology and evolution 13 34491357
2019 Depletion of PRDM9 enhances proliferation, migration and chemotaxis potentials in human periodontal ligament stem cells. Connective tissue research 13 31096797
2023 Identification of nonhistone substrates of the lysine methyltransferase PRDM9. The Journal of biological chemistry 12 36972790
2016 Evidence of positive selection and concerted evolution in the rapidly evolving PRDM9 zinc finger domain in goats and sheep. Animal genetics 12 27621101
2017 Discovery and characterisation of the automethylation properties of PRDM9. The Biochemical journal 11 28126738
2016 Zinc Finger Domain of the PRDM9 Gene on Chromosome 1 Exhibits High Diversity in Ruminants but Its Paralog PRDM7 Contains Multiple Disruptive Mutations. PloS one 11 27203728
2012 Evaluation of PRDM9 variation as a risk factor for recurrent genomic disorders and chromosomal non-disjunction. Human genetics 11 22643917
2022 The KRAB Domain of ZNF10 Guides the Identification of Specific Amino Acids That Transform the Ancestral KRAB-A-Related Domain Present in Human PRDM9 into a Canonical Modern KRAB-A Domain. International journal of molecular sciences 10 35162997
2019 PRDM9 and the evolution of recombination hotspots. Theoretical population biology 10 30660607
2025 PRDM9 drives the location and rapid evolution of recombination hotspots in salmonid fish. PLoS biology 9 39761307
2024 Bridging the gap between the evolutionary dynamics and the molecular mechanisms of meiosis: A model based exploration of the PRDM9 intra-genomic Red Queen. PLoS genetics 9 38768268
2020 Meiotic epigenetic factor PRDM9 impacts sperm quality of hybrid mice. Reproduction (Cambridge, England) 8 32272448
2018 Prenatal diagnosis of a familial 5p14.3-p14.1 deletion encompassing CDH18, CDH12, PMCHL1, PRDM9 and CDH10 in a fetus with congenital heart disease on prenatal ultrasound. Taiwanese journal of obstetrics & gynecology 8 30342662
2010 PRDM9 sticks its zinc fingers into recombination hotspots and between species. F1000 biology reports 8 20948797
2022 Genic and chromosomal components of Prdm9-driven hybrid male sterility in mice (Mus musculus). Genetics 7 35924978
2016 Variation in the Zinc Finger of PRDM9 is Associated with the Absence of Recombination along Nondisjoined Chromosomes 21 of Maternal Origin. Journal of Down Syndrome & chromosome abnormalities 7 28702511
2019 PRDM9 forms a trimer by interactions within the zinc finger array. Life science alliance 6 31308055
2019 Bos taurus-indicus hybridization correlates with intralocus sexual-conflict effects of PRDM9 on male and female fertility in Holstein cattle. BMC genetics 6 31462216
2016 The pioneering role of PRDM9 indel mutations in tarsier evolution. Scientific reports 6 27698394
2013 The complex binding of PRDM9. Genome biology 6 23651476
2023 The RNA-binding protein FUS/TLS interacts with SPO11 and PRDM9 and localize at meiotic recombination hotspots. Cellular and molecular life sciences : CMLS 5 36967403
2023 Cancer Associated PRDM9: Implications for Linking Genomic Instability and Meiotic Recombination. International journal of molecular sciences 5 38003713
2024 Natural variation in the zinc-finger-encoding exon of Prdm9 affects hybrid sterility phenotypes in mice. Genetics 4 38217871
2023 The Recombination Hotspot Paradox: Co-evolution between PRDM9 and its target sites. Theoretical population biology 4 37451508
2022 Evolution of the recombination regulator PRDM9 in minke whales. BMC genomics 4 35296233
2015 How Y357F, Y276F mutants affect the methylation activity of PRDM9: QM/MM MD and free energy simulations. Journal of molecular modeling 4 25903303