ArticleEpigenetics & chromatin2015
Affinity-seq detects genome-wide PRDM9 binding sites and reveals the impact of prior chromatin modifications on mammalian recombination hotspot usage.
Article in Epigenetics & chromatin, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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53 citing papers in PubMed, 87 citations in OpenAlex.
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- Footprint-seq: a simple method to quantitatively mapbioRxiv : the preprint server for biology · 2026Article
- Single-cell long-read Hi-C, scNanoHi-C2, details 3D genome reorganization in embryonic-stage germ cells.Nature structural & molecular biology · 2025Article
- Deciphering meiotic chromatin organization by SYCP3.Nucleic acids research · 2025Article
- A Pedigree-Based Map of Crossovers and Noncrossovers in Aye-Ayes (Daubentonia madagascariensis).Genome biology and evolution · 2025Article
- A pedigree-based map of crossovers and non-crossovers in aye-ayes (bioRxiv : the preprint server for biology · 2024Article
- Natural variation in the zinc-finger-encoding exon of Prdm9 affects hybrid sterility phenotypes in mice.Genetics · 2024Article
- Novel Insights into the Landscape of Crossover and Noncrossover Events in Rhesus Macaques (Macaca mulatta).Genome biology and evolution · 2024Article
- Single-cell multi-omics sequencing of human spermatogenesis reveals a DNA demethylation event associated with male meiotic recombination.Nature cell biology · 2023Article
- On the dependent recognition of some long zinc finger proteins.Nucleic acids research · 2023Article
- A-MYB and BRDT-dependent RNA Polymerase II pause release orchestrates transcriptional regulation in mammalian meiosis.Nature communications · 2023Article
- Epigenetic regulator Cfp1 safeguards male meiotic progression by regulating meiotic gene expression.Experimental & molecular medicine · 2022Article
- Differential effects of two catalytic mutations on full-length PRDM9 and its isolated PR/SET domain reveal a case of pseudomodularity.Genetics · 2021Article
- Genome-wide variability in recombination activity is associated with meiotic chromatin organization.Genome research · 2021Article
- Article
- Rat PRDM9 shapes recombination landscapes, duration of meiosis, gametogenesis, and age of fertility.BMC biology · 2021Article
- Sperm acrosome overgrowth and infertility in mice lacking chromosome 18 pachytene piRNA.PLoS genetics · 2021Article
- Cataloging HumanFrontiers in cell and developmental biology · 2021Article
- 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 · 2021Article
- Sexual dimorphism in the meiotic requirement for PRDM9: A mammalian evolutionary safeguard.Science advances · 2020Article
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
Abstract
backgroundGenetic recombination plays an important role in evolution, facilitating the creation of new, favorable combinations of alleles and the removal of deleterious mutations by unlinking them from surrounding sequences. In most mammals, the placement of genetic crossovers is determined by the binding of PRDM9, a highly polymorphic protein with a long zinc finger array, to its cognate binding sites. It is one of over 800 genes encoding proteins with zinc finger domains in the human genome.
resultsWe report a novel technique, Affinity-seq, that for the first time identifies both the genome-wide binding sites of DNA-binding proteins and quantitates their relative affinities. We have applied this in vitro technique to PRDM9, the zinc-finger protein that activates genetic recombination, obtaining new information on the regulation of hotspots, whose locations and activities determine the recombination landscape. We identified 31,770 binding sites in the mouse genome for the PRDM9(Dom2) variant. Comparing these results with hotspot usage in vivo, we find that less than half of potential PRDM9 binding sites are utilized in vivo. We show that hotspot usage is increased in actively transcribed genes and decreased in genomic regions containing H3K9me2/3 histone marks or bound to the nuclear lamina.
conclusionsThese results show that a major factor determining whether a binding site will become an active hotspot and what its activity will be are constraints imposed by prior chromatin modifications on the ability of PRDM9 to bind to DNA in vivo. These constraints lead to the presence of long genomic regions depleted of recombination.
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