The meiotic synaptonemal complex is assembled from independently regulated gene programmes
- 1University of Liverpool
Abstract
Synaptonemal complex (SC) proteins assemble a highly specialised chromosome structure during meiosis and are considered products of a coordinated germline programme that is silenced in somatic cells. Here, we show that this binary model does not describe the regulation of the eight core mammalian SC genes. Despite assembling into a single molecular complex, SC genes follow distinct regulatory trajectories from meiotic entry through SC disassembly. Their activation is staggered, transcripts and proteins persist with different kinetics after SC disassembly begins in late pachytene, and RNA abundance generally fails to predict protein abundance, revealing extensive regulation between transcription and protein accumulation. Integrating promoter state, nascent transcription, RNA and translational measurements identified gene-specific regulatory strategies rather than a shared SC regulatory mechanism. This independence extends beyond the germline and explains how cancers can express individual SC genes. In cancer cells, individual SC loci occupy distinct transcriptional states, including conventional promoter activation, alternative promoter usage, cell-cycle-dependent transcription and promoter competence without detectable productive transcription. DNA methylation can repress individual SC promoters but does not define a common somatic OFF state, while related transcriptional inputs produce different downstream RNA outputs between SC genes. Unexpectedly, single-cell transcriptomes across healthy mouse and human tissues reveal that somatic SC expression is not restricted to cancer: individual SC genes show reproducible associations with specific cell populations, including fibroblasts, myeloid cells, Schwann cells and progenitors. Thus, SC proteins are neither expressed nor silenced as an obligately coupled gene set. We propose that SC identity emerges from the temporally restricted convergence and assembly of independently regulated genes and proteins during meiosis, while their regulatory autonomy permits individual components to be retained or redeployed in normal somatic cells and cancer. The SC therefore represents an emergent molecular state: its components retain distinct regulatory identities, while their transient convergence during meiotic prophase generates a structure and function that none defines individually.
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BibTeX
@misc{brennan2026meiotic,
title = {{The meiotic synaptonemal complex is assembled from independently regulated gene programmes}},
author = {L. C. Brennan and C. J. Fawcett and I. F. Sou and A. D. Bates and A. Saifudeen and M. A. Ikert and A. G. Ginesta and B. Hammond and U. L. McClurg},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.09.750351},
url = {https://www.biorxiv.org/content/10.64898/2026.09.09.750351v1},
note = {CC BY-NC},
}
RIS
TY - UNPB
TI - The meiotic synaptonemal complex is assembled from independently regulated gene programmes
AU - L. C. Brennan
AU - C. J. Fawcett
AU - I. F. Sou
AU - A. D. Bates
AU - A. Saifudeen
AU - M. A. Ikert
AU - A. G. Ginesta
AU - B. Hammond
AU - U. L. McClurg
PY - 2026
DA - 2026/09/09
PB - bioRxiv
DO - 10.64898/2026.09.09.750351
UR - https://www.biorxiv.org/content/10.64898/2026.09.09.750351v1
AB - Synaptonemal complex (SC) proteins assemble a highly specialised chromosome structure during meiosis and are considered products of a coordinated germline programme that is silenced in somatic cells. Here, we show that this binary model does not describe the regulation of the eight core mammalian SC genes. Despite assembling into a single molecular complex, SC genes follow distinct regulatory trajectories from meiotic entry through SC disassembly. Their activation is staggered, transcripts and proteins persist with different kinetics after SC disassembly begins in late pachytene, and RNA abundance generally fails to predict protein abundance, revealing extensive regulation between transcription and protein accumulation. Integrating promoter state, nascent transcription, RNA and translational measurements identified gene-specific regulatory strategies rather than a shared SC regulatory mechanism. This independence extends beyond the germline and explains how cancers can express individual SC genes. In cancer cells, individual SC loci occupy distinct transcriptional states, including conventional promoter activation, alternative promoter usage, cell-cycle-dependent transcription and promoter competence without detectable productive transcription. DNA methylation can repress individual SC promoters but does not define a common somatic OFF state, while related transcriptional inputs produce different downstream RNA outputs between SC genes. Unexpectedly, single-cell transcriptomes across healthy mouse and human tissues reveal that somatic SC expression is not restricted to cancer: individual SC genes show reproducible associations with specific cell populations, including fibroblasts, myeloid cells, Schwann cells and progenitors. Thus, SC proteins are neither expressed nor silenced as an obligately coupled gene set. We propose that SC identity emerges from the temporally restricted convergence and assembly of independently regulated genes and proteins during meiosis, while their regulatory autonomy permits individual components to be retained or redeployed in normal somatic cells and cancer. The SC therefore represents an emergent molecular state: its components retain distinct regulatory identities, while their transient convergence during meiotic prophase generates a structure and function that none defines individually.
ER -