Max Greenberg (Institut Jacques Monod, CNRS, Université Paris Cité, Paris, France)
IGH Seminar room 1st floor
Non-canonical functions of DNA methylation during epigenetic reprogramming in mammals
Immediately after fertilization, mammalian embryos undergo a dramatic reshaping of the epigenome as the embryo transitions from the zygote into the pluripotent cells primed for lineage commitment. This is best exemplified by 5-cytosine DNA methylation (5meC) reprogramming, as the gametic patterns are largely erased, and the embryonic genome undergoes a wave of de novo DNA methylation. Moreover, once 5meC patterns are established, mechanisms faithfully maintain the mark across cell division. Thus, there is latent potential for DNA methylation deposited in the early embryo to exhibit a lifelong effect.
DNA methylation is a modification that is typically associated with gene repression at repetitive elements and at a minority of protein coding genes. However, the methyl-mark is broadly distributed throughout the genome, including actively transcribed regions. In our lab, we are interested in the non-canonical functions of DNA methylation in genome regulation. These include the interplay with other chromatin pathways, the influence on chromatin architecture, and the role at cis regulatory elements. Pertinently, in all cases we have an agnostic prediction of whether 5meC has a positive, negative, or neutral impact on gene expression.
To interrogate these aforementioned non-canonical roles, we are primarily utilizing a cell-based differentiation system that recapitulates the embryonic wave of 5meC establishment, employing both wild-type and mutant cell lines that are deficient for DNA methylation machinery. We are synthesizing genome-wide assays with a precision epigenome editing approach in order to address the locus-specific impact of DNA methylation. Our ultimate goal is to gain a clear understanding of the profound epigenetic consequences of DNA methylation on this window of development, which occurs in the first week of mouse embryogenesis, and the second of human, but the repercussions of which can ripple throughout life. Our latest results will be discussed.
Epigenetics workshop-Seminar Serie 7th-15th Nov 2022
The Nuclear architecture in physiology - Charlène Boumendil - and the Chromatin and cell biology - Giacomo CAVALLI - are thrilled to announce our next workshop in Epigenetics, from November 07th to November 15th.
We have a fantastic speakers line up (see below and attached flyer), all seminars will take place at 2pm in the Genopolys Amphitheatre.
7th Nov, 2pm: Dr Petra Hajkova, MRC London Institute of Medical Sciences - UK Stability and erasure of epigenetic information in vivo and in vitro
8th Nov, 2pm: Dr Caroline Dean, John Innes Centre - UK Cold-induced epigenetic silencing
9th Nov, 2pm: Dr Jop Kind, Hubrecht Institute - Netherlands The chromatin landscape during early embryo development at single-cell resolution
10th Nov, 2pm: Dr Geneviève Almouzni, Institut Curie - France Histone H3 variants and chaperones on the chromatin dance-floor
14th Nov, 2pm: Dr Remi Terranova, Novartis, Novartis Institutes for BioMedical Research - Switzerland Basic Principles of Preclinical Safety Assessment- Therapeutic Modulation of the Epigenome
15th Nov, 2pm: Dr Maud Borensztein, Institute of Molecular Genetics of Montpellier - France X-chromosome dynamics during female mouse development
Dr. Mireille Betermier (Director of research at CNRS- Institute for Integrative Biology of the Cell, Department of Genome Biology Université Paris-Saclay)
Amphitheater of Genopolys
Programmed DNA elimination in the ciliate Paramecium: from molecular mechanism to evolution
With its nuclear dimorphism, the ciliate Paramecium provides a powerful unicellular model to study how eukaryotic genomes cope with transposable elements (TEs). During evolution, the Paramecium germline genome, hosted in two transcriptionally silent micronuclei, has been continuously colonized by TEs, including in essential coding regions. Functional gene expression relies on the programmed elimination of parasitic sequences, which takes place at each sexual cycle in the transcription-prone somatic macronucleus. While most TEs are eliminated in a heterogeneous manner, excision of ~45,000 Tc1/mariner-related Internal Eliminated Sequences (IESs) is precise. It is carried out by a core machinery composed of domesticated PiggyBac transposases associated with double-strand break repair proteins. Except for a subset of IESs, which will be discussed during my talk, programmed DNA elimination is guided by non-coding RNAs (ncRNAs) and repressive chromatin marks. More about Dr. Mireille Betermier https://www.i2bc.paris-saclay.fr/equipe-programmed-genome-rearrangements/