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Concept

Gène soumis à empreinte

Résumé

On dit d'un gène qu'il est soumis à l'empreinte parentale lorsque, chez les organismes diploïdes, la copie héritée de la mère et la copie héritée du père ne sont pas exprimées de la même manière. En règle générale, l'une des deux copies du gène est totalement éteinte alors que l'autre est active . Les gènes soumis à l'empreinte parentale sont essentiellement impliqués dans le développement. Aujourd'hui on ne connait des gènes soumis à l'empreinte que chez les mammifères et les plantes à fleur. D'un point de vue moléculaire, l'empreinte parentale est due à l'apposition de marques épigénétiques dans les cellules germinales des parents. Ces marques peuvent par exemple conduire à la répression d'un gène. L'empreinte parentale est due à une différence entre les marques épigénétiques sur la copie d'un gène héritée de la mère et la copie d'un gène héritée du père. Historique et découverte Durant les années 1980, des chercheurs montrent qu'un embryon de souris issu artificielleme

Source officielle

https://fr.wikipedia.org/wiki/G%C3%A8ne_soumis_%C3%A0_empreinte

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KRAB'n'KAP, DNA methylation and epigenetic memory

Andrea Coluccio

The KZFP/KAP1 (Krüppel associated box zinc finger proteins/KRAB-associated protein 1) complex is a transcriptional repressor that triggers the deposition of heterochromatin (H3K9me3) and DNA methylation. The main targets of the KZFP/KAP1 complex are transposable elements (TEs), which are generally maintained transcriptionally inactive to avoid retrotransposition and preserve genomic stability, and imprinting control regions (ICRs), where DNA methylation is protected to ensure proper parent-of-origin specific expression of crucial developmental genes. The role of the KZFP/KAP1 system in forming a heterochromatic environment is of particular relevance during the wave of genome-wide epigenetic reprogramming that takes place in the early embryo between fertilization and implantation. During these stages, TEs and ICRs are amongst the few sequences that retain the epigenetic information inherited from the gametes. While the importance of KZFP/KAP1 in maintenance of imprinting and TE silencing is well established, the mechanisms by which KAP1 counteracts demethylation and interacts with this epigenetically unstable environment to regulate TEs are still largely unknown. In this work, we uncover the complex interplay between KAP1, DNA methylation and active demethylation in maintaining imprinting and regulating TE expression in naïve embryonic stem cells. We first confirmed that KAP1 was able to bind and repress TEs in absence of DNA methylation. We then demonstrated that the KZFP/KAP1 complex was required to maintain heterochromatin and DNA methylation at ICRs and TEs, and was able to protect these sequences from active demethylation. We comprehensively characterized the responsiveness of TEs to removal of KAP1 in absence of DNA methylation and active demethylation, which unveiled a complex, multi-layered and integrant-specific regulation for these elements. ZFP57 is known to recruit KAP1 on ICRs, but here we identified ZNF445 as a second KZFP that specifically binds ICRs both in human and mouse. We found that ZNF445 regulates imprinting differentially in human versus murine embryonic stem cells. Our findings suggest for the first time that two different KZFPs could have evolved with species-specific roles in imprinting regulation. The high degree of conservation of ZNF445 in the human population argues in favour of a previously unsuspected critical role for this protein in development. This work provides useful insights in the role of KAP1 and its KZFPs partners both in preserving epigenetic memory and in transposon silencing during early development.

EPFL2017

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The enhancement of DNA fragmentation in a bench top ultrasonic water bath with needle-induced air bubbles: Simulation and experimental investigation

Martinus Gijs, Thomas Lehnert, Yang Liu, Lin Sun

Shearing DNA to a certain size is the first step in many medical and biological applications, especially in next-generation gene sequencing technology. In this article, we introduced a highly efficient ultrasonic DNA fragmentation method enhanced by needle-induced air bubbles, which is easy to operate with high throughput. The principle of the bubble-enhanced sonication system is introduced and verified by flow field and acoustic simulations and experiments. Lambda DNA long chains and mouse genomic DNA short chains are used in the experiments for testing the performance of the bubble-enhanced ultrasonic DNA fragmentation system. Air bubbles are an effective enhancement agent for ultrasonic DNA fragmentation; they can obviously improve the sound pressure level in the whole solution, thus, achieving better absorption of ultrasound energy. Growing bubbles also have a stretched function on DNA molecule chains and form a huge pressure gradient in the solution, which is beneficial to DNA fragmentation. Purified lambda DNA is cut from 48.5 to 2 kbp in 5 min and cut to 300 bp in 30 min. Mouse genomic DNA (asymptotic to 1400 bp) decreases to 400 bp in 5 min and then reduces to 200 bp in 30 min. This bubble-enhanced ultrasonic method enables widespread access to genomic DNA fragmentation in a standard ultrasonic water bath for many virus sequencing demands even without good medical facilities. Published under an exclusive license by AIP Publishing.

AIP Publishing2022

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Modelling the evolution of biological networks is a major challenge. Biological networks are usually represented as graphs; evolutionary events include addition and removal of vertices and edges, but also duplication of vertices and their associated edges. Since duplication is viewed as a primary driver of genomic evolution, recent work has focused on duplication-based models. Missing from these models is any embodiment of modularity, a widely accepted attribute of biological networks. Some models spontaneously generate modular structures, but none is known to maintain and evolve them. We describe NEMo (Network Evolution with Modularity), a new model that embodies modularity. NEMo allows modules to emerge and vanish, to fission and merge, all driven by the underlying edge-level events using a duplication-based process. We introduce measures to compare biological networks in terms of their modular structure and use them to compare NEMo and existing duplication-based models and to compare both generated and published networks.

Springer Int Publishing Ag2016

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KRAB'n'KAP, DNA methylation and epigenetic memory

Andrea Coluccio

EPFL2017