Related Experiment Video
Updated: Oct 2, 2026
Immunohistochemical Detection of 5-Methylcytosine and 5-Hydroxymethylcytosine in Developing and Postmitotic Mouse Retina
Published on: August 29, 2018
Transvection effects involving DNA methylation during meiosis in the mouse
Minoo Rassoulzadegan1, Marc Magliano, François Cuzin
1Unité 470, Institut National de la Santé et de la Recherche Médicale, Université de Nice-Sophia Antipolis, Nice, France.
Abstract:
High efficiencies of recombination between LoxP elements were initially recorded when the Cre recombinase was expressed in meiotic spermatocytes. However, it was unexpectedly found that LoxP recombination fell to very low values at the second generation of mice expressing Cre during meiosis. The inability of the LoxP elements to serve as recombination substrates was correlated with cytosine methylation, initially in LoxP and transgene sequences, but later extending for distances of at least several kilobases into chromosomal sequences. It also affected the allelic locus, implying a transfer of structural information between alleles similar to the transvection phenomenon described in Drosophila. Once initiated following Cre-LoxP interaction, neither cis-extension nor transvection of the methylated state required the continuous expression of Cre, as they occurred both in germinal and somatic cells and in the fraction of the offspring that had not inherited the Sycp1-Cre transgene. Therefore, these processes depend on a physiological mechanism of establishment and extension of an epigenetic state, for which they provide an experimental model.
Insights
Cre-LoxP recombination efficiency decreased across generations in mice due to cytosine methylation. This epigenetic state spread to neighboring DNA, demonstrating a novel mechanism for epigenetic inheritance.
Area of Science:
- Epigenetics
- Genetics
- Molecular Biology
Background:
- Cre-LoxP recombination is a widely used tool in genetic engineering.
- High recombination efficiencies were initially observed in meiotic spermatocytes.
Purpose of the Study:
- Investigate the unexpected decline in LoxP recombination efficiency in subsequent generations.
- Characterize the molecular mechanisms underlying this phenomenon.
Main Methods:
- Utilized Cre-LoxP system in mice with Cre expression during meiosis.
- Analyzed DNA methylation patterns in LoxP and surrounding sequences.
- Examined epigenetic state inheritance in offspring.
Main Results:
- LoxP recombination efficiency significantly decreased by the second generation.
- Cytosine methylation of LoxP and transgene sequences correlated with reduced recombination.
- Methylation extended into chromosomal sequences and affected allelic loci (transvection-like phenomenon).
- Epigenetic state establishment and spread occurred independently of continuous Cre expression.
Conclusions:
- Cre-LoxP recombination can initiate a heritable epigenetic state characterized by cytosine methylation.
- This epigenetic state can spread cis and trans to affect recombination.
- The findings reveal a physiological mechanism for epigenetic state establishment and propagation, offering a model for epigenetic inheritance studies.
Related Concept Videos
03:09Meiosis I
Prophase I is the most extended and complex step of meiosis I characterized by synapsis, chromosome pairing, and recombination of the homologous chromosomes. This process is facilitated by a proteinaceous structure called the...
03:20Meiosis I
02:57Meiosis vs. Mitosis
Before the start of mitosis and meiosis I, the cell synthesizes DNA, resulting in two homologous copies of each chromosome. DNA synthesis is...
02:23Meiosis II
02:02Meiosis II
The timing and cell division patterns of meiosis differ between males and females. In male meiosis, the centrosomes are part of the formation of the meiotic spindle. However, in oocytes, including that of humans, Drosophila,...
02:32Position-effect Variegation