Chromatin and Genome Silencing
Precise regulation of gene expression is critical for life. Indeed, in certain conditions some genes need to be expressed into functional molecules such as proteins and in other conditions those or other genes need to be silenced to guarantee the proper functions of cells and organisms during development and in response to the environment. Misregulation of gene expression can lead to developmental defects and diseases.
Regulation of gene expression relies on three main levels, the transcriptional (DNA>RNA), post-transcriptional level (RNA regulation), and translational (protein level regulation).
In the lab, we are interested on the epigenetics mechanisms underlying genome silencing at the transcriptional and post-transcriptional levels. Those two levels are regulated by many processes including through the activity of transcription factors, RNA-binding proteins and chromatin modifying enzymes. Chromatin which is composed of DNA and proteins including histones which can be modified. Histone modifications confer an additional layer of regulation that fine tune expression at both transcriptional and post-transcriptional levels. Our favorite model organisms are Drosophila and C. elegans, but we also work on mammalian cells including human and primary murine cells when necessary. Using a combination of microscopy, biochemical, molecular biology, genetics and genomics analysis our main research interests focus on:
1) Silencing of transposable elements
2) Silencing of H3K27me3-enriched chromatin via RNA degradation
Silencing of transposable Elements (ETs)
Heterochromatin and Polycomb-marked gene Silencing by RNA decay
- Douaa Moussalem, Benoit Augé, Luisa Di Stefano, Dani Osman, Vanessa Gobert and Marc Haenlin1.
Two Isoforms of serpent Containing Either One or Two GATA Zinc Fingers Provide Functional Diversity During Drosophila Development
Frontiers in Cell and Developmental Biology
- Mattout A, Gaidatzis D, Padeken J, Schmid CD, Aeschimann F, Kalck V, Gasser SM. .
LSM2-8 and XRN-2 contribute to the silencing of H3K27me3-marked genes through targeted RNA decay.
Nat Cell Biol.
2020 May To understand this work in 5 minutes, look at the presentation. http://sciversal.com/Home/MinipubPlayer/?slideId=1072
- Harr JC, Schmid CD, Muñoz-Jiménez C, Romero-Bueno R, Kalck V, Gonzalez-Sandoval A, Hauer MH, Padeken J, Askjaer P, Mattout A*, Gasser SM..
Loss of an H3K9me anchor rescues laminopathy-linked changes in nuclear organization and muscle function in an Emery-Dreifuss muscular dystrophy model
2020 Apr doi: 10.1101/gad.332213.119 *Corresponding Author
- Mattout A, Gaidatzis D, Kalck V, Gasser SM..
A Nuclear RNA Degradation Pathway Helps Silence Polycomb/H3K27me3-Marked Loci in Caenorhabditis elegans.
Cold Spring Harb Symp Quant Biol.
2020 Apr DOI: 10.1101/sqb.2019.84.040238
- Julie M.J. Lepesant, Carole Iampietro, Eugenia Galeota, Benoit Auge, Marion Aguirrenbengoa, Clementine Merce, Camille Chaubet, Vincent Rocher, Marc Haenlin, Lucas Waltzer, Mattia Pelizzola and Luisa Di Stefano.
A dual role of dLsd1 in oogenesis: regulating developmental genes and repressing transposons
Nucleic Acids Research, 2020 Feb 20;48(3):1206-1224
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