Login / Signup

Epigenetic Dysregulation of Mammalian Male Meiosis Caused by Interference of Recombination and Synapsis.

Roberto de la FuenteFlorencia PrattoAbrahan Hernández-HernándezMarcia ManterolaPablo López-JiménezRocío GómezAlberto VieraMaría Teresa ParraAnna KouznetsovaR Daniel Camerini-OteroJesús Page
Published in: Cells (2021)
Meiosis involves a series of specific chromosome events, namely homologous synapsis, recombination, and segregation. Disruption of either recombination or synapsis in mammals results in the interruption of meiosis progression during the first meiotic prophase. This is usually accompanied by a defective transcriptional inactivation of the X and Y chromosomes, which triggers a meiosis breakdown in many mutant models. However, epigenetic changes and transcriptional regulation are also expected to affect autosomes. In this work, we studied the dynamics of epigenetic markers related to chromatin silencing, transcriptional regulation, and meiotic sex chromosome inactivation throughout meiosis in knockout mice for genes encoding for recombination proteins SPO11, DMC1, HOP2 and MLH1, and the synaptonemal complex proteins SYCP1 and SYCP3. These models are defective in recombination and/or synapsis and promote apoptosis at different stages of progression. Our results indicate that impairment of recombination and synapsis alter the dynamics and localization pattern of epigenetic marks, as well as the transcriptional regulation of both autosomes and sex chromosomes throughout prophase-I progression. We also observed that the morphological progression of spermatocytes throughout meiosis and the dynamics of epigenetic marks are processes that can be desynchronized upon synapsis or recombination alteration. Moreover, we detected an overlap of early and late epigenetic signatures in most mutants, indicating that the normal epigenetic transitions are disrupted. This can alter the transcriptional shift that occurs in spermatocytes in mid prophase-I and suggest that the epigenetic regulation of sex chromosomes, but also of autosomes, is an important factor in the impairment of meiosis progression in mammals.
Keyphrases
  • dna damage
  • gene expression
  • dna repair
  • dna methylation
  • genome wide
  • oxidative stress
  • transcription factor
  • copy number
  • heat shock
  • functional connectivity
  • drug induced
  • heat stress