Coarsening dynamics can explain meiotic crossover patterning in both the presence and absence of the synaptonemal complex
- John Innes Centre, United Kingdom
Abstract
The shuffling of genetic material facilitated by meiotic crossovers is a critical driver of genetic variation. Therefore, the number and positions of crossover events must be carefully controlled. In Arabidopsis, an obligate crossover and repression of nearby crossovers on each chromosome pair are abolished in mutants that lack the synaptonemal complex (SC), a conserved protein scaffold. We use mathematical modelling and quantitative super-resolution microscopy to explore and mechanistically explain meiotic crossover pattering in Arabidopsis lines with full, incomplete or abolished synapsis. For zyp1 mutants, which lack an SC, we develop a coarsening model in which crossover precursors globally compete for a limited pool of the pro-crossover factor HEI10, with dynamic HEI10 exchange mediated through the nucleoplasm. We demonstrate that this model is capable of quantitatively reproducing and predicting zyp1 experimental crossover patterning and HEI10 foci intensity data. Additionally, we find that a model combining both SC- and nucleoplasm-mediated coarsening can explain crossover patterning in wild-type Arabidopsis and in pch2 mutants, which display partial synapsis. Together, our results reveal that regulation of crossover patterning in wild-type Arabidopsis and SC defective mutants likely act through the same underlying coarsening mechanism, differing only in the spatial compartments through which the pro-crossover factor diffuses.
Data availability
Imaging data associated with this study are available at doi.org/10.6084/m9.figshare.19650249.v1, doi.org/10.6084/m9.figshare.19665810.v1 and doi.org/10.6084/m9.figshare.21989732. Custom Python scripts for data analysis are available at https://github.com/jfozard/hei10_zyp1.
-
The synaptonemal complex imposes crossover interference and heterochiasmy in ArabidopsisProceedings of the National Academy of Sciences 118:e2023613118.
Article and author information
Author details
Funding
Biotechnology and Biological Sciences Research Council (BB/V005774/1)
- Chris Morgan
Biotechnology and Biological Sciences Research Council (BB/P013511/1)
- Martin Howard
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2023, Fozard et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
Metrics
-
- 1,329
- views
-
- 246
- downloads
-
- 30
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Coarsening dynamics can explain meiotic crossover patterning in both the presence and absence of the synaptonemal complex
eLife 12:e79408.
https://doi.org/10.7554/eLife.79408
Further reading
-
- Genetics and Genomics
- Neuroscience
Thermal nociception in Caenorhabditis elegans is regulated by the Ca²+/calmodulin-dependent protein kinase CMK-1, but its downstream effectors have remained unclear. Here, we combined in vitro kinase assays with mass-spectrometry-based phosphoproteomics to identify hundreds of CMK-1 substrates, including the calcineurin A subunit TAX-6, phosphorylated within its conserved regulatory domain. Genetic and pharmacological analyses reveal multiple antagonistic interactions between CMK-1 and calcineurin signaling in modulating both naive thermal responsiveness and adaptation to repeated noxious stimuli. Cell-specific manipulations indicate that CMK-1 acts in AFD and ASER thermo-sensory neurons, while TAX-6 functions in FLP thermo-sensory neurons and downstream interneurons. Since CMK-1 and TAX-6 act in distinct cell types, the phosphorylation observed in vitro might not directly underlie the behavioral phenotype. Instead, the opposing effects seem to arise from their distributed roles within the sensory circuit. Overall, our study provides (1) a resource of candidate CMK-1 targets for further dissecting CaM kinase signaling and (2) evidence of a previously unrecognized, circuit-level antagonism between CMK-1 and calcineurin pathways. These findings highlight a complex interplay of signaling modules that modulate thermal nociception and adaptation, offering new insights into potentially conserved mechanisms that shape nociceptive plasticity and pain (de)sensitization in more complex nervous systems.
-
- Genetics and Genomics
Isocitrate dehydrogenase 1 (IDH1) is the key enzyme that can modulate cellular metabolism, epigenetic modification, and redox homeostasis. Gain-of-function mutations and decreased expression of IDH1 have been demonstrated to be associated with pathogenesis of various myeloid malignancies characterized by ineffective erythropoiesis, such as acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). However, the function and mechanism of IDH1 in human erythropoiesis still remains unclear. Here, utilizing the human erythropoiesis system, we present an evidence of IDH1-mediated chromatin state reprogramming besides its well-characterized metabolism effects. We found that knockdown IDH1 induced chromatin reorganization and subsequently led to abnormalities biological events in erythroid precursors, which could not be rescued by addition of reactive oxygen species (ROS) scavengers or supplementation of α-ketoglutarate (α-KG).We further revealed that knockdown IDH1 induces genome-wide changes in distribution and intensity of multiple histone marks, among which H3K79me3 was identified as a critical factor in chromatin state reprogramming. Integrated analysis of ChIP-seq, ATAC-seq, and RNA-seq recognized that SIRT1 was the key gene affected by IDH1 deficiency. Thus, our current work provided novel insights for further clarifying fundamental biological function of IDH1 which has substantial implications for an in-depth understanding of pathogenesis of diseases with IDH1 dysfunction and accordingly development of therapeutic strategies.
