Taux de GC | EPFL Graph Search

Le taux de GC (ou pourcentage de GC, ou coefficient de Chargaff) d'une séquence d'ADN est défini comme la proportion de bases nucléiques de cette séquence étant soit une guanine (G), soit une cytosine (C). Il existe deux bases nucléiques supplémentaires, l'adénine (A) et la thymine (T), entrant dans la composition de l'ADN. De plus, la cytosine est toujours liée à la guanine, et l'adénine est toujours liée à la thymine. Ainsi, le taux de GC exprime aussi le pourcentage de liaisons G-C dans la molécule d'ADN. Calcul du taux de GC Le taux de GC d'une séquence est calculé d'après la formule: :\cfrac{(G+C)}{(A+T+G+C)}\times\ 100 où G désigne le nombre de guanines dans la séquence, A le nombre d'adénines, C celui de cytosines et T celui de thymines. Il existe aussi d'autres calculs plus particuliers du taux de GC. Les taux de GC1, GC2 et GC3 sont respectivement les taux de GC des premières, deuxièmes et troisièmes positions des codons. Ainsi, pour déterminer le G

Polycomb Recruitment and Targeting in Mammals

Patrick Schorderet

Polycomb- (PcG) and trithorax (trxG) group proteins are essential components in the regulation of multiple developmental regulators. In particular, during early stages, they act as chromatin modifiers in such a way as to set and maintain the transcriptional status of Hox genes. Little is known, in vertebrates, concerning the modalities of PcG binding to their target sites. One possibility is that they are recruited, in a synergistic manner, through their binding to specific DNA regulatory elements to control spatial and temporal restriction of Hox genes by trimethylating lysine 27 on histone 3 (H3K27me3). Whereas these DNA sequences, referred to as polycomb response elements (PREs), have been identified in Drosophila, their existence in mammals remains to be clearly demonstrated. In this work, we aim to decipher the means by which polycomb repressive complexes (PRCs) are recruited to PREs during early mouse development and focus on the HoxD cluster, a genomic segment that is amongst the most heavily covered by H3K27me3 marks in embryonic stem (ES) cells and where one of the few vertebrate PRE has been previously reporter. We describe relatively small DNA sequences lying within the HoxD locus that are necessary and sufficient for the tethering of polycomb to ectopic loci. These elements work synergistically to form a fully functional repressive domain. Moreover, we show that a sequence with high GC content, although not necessary for the initial recruitment of PRC per se, may stabilize the link between the complex and the underlying DNA. Finally, we propose a model for the evolution of polycomb targets and discuss the emergence of diverging recruitment mechanisms amongst Drosophila, mice and humans.

EPFL2013

Landscape of data repositories and platforms

Eliane Ninfa Blumer, Miriam Braskova, Francesco Varrato, Charlotte Gisèle Weil

Scholarly Communication is still shifting from papers to richer content, as for instance research data and code. Data dissemination has a crucial role and yet it is in its infancy, with visible fragmentation and too many unknowns for researchers to get onboard. With our work, we want to mitigate this situation and help researchers decide which platforms are best suited to disseminate their data and code. The table we elaborated is based on multiple feedback from EPFL researchers, and its purpose is both to capture the variety of use-cases, and to guide researchers to make their choice. This poster is principally conceived for colleagues working in university services related to Open Science and Research Data Management, to provide them with an example of collaboration that might be reproduced in their institutions, and to create awareness on the challenges that such an endeavor entails. In this publication, we also include the current version of the comparative table of data dissemination solutions.

2021

KRAB zinc finger protein-mediated control of transposon-embedded regulatory sequences from human germline to early embryos

Alexandra Iouranova

Transposable elements (TEs), also called jumping genes, are genetic elements capable of changing their position within the genome of their host. They make up large fractions of genomes, including 45% of human DNA content, according to current estimates. Some of these elements are of retroviral origin and are known as endogenous retroviruses (ERVs). Long terminal repeats (LTRs) of ERVs, like other TEs, influence host gene expression in various ways. They can for example create new promoters, enhancers or imprinted regions upon integration. As ERVs derive from a germline infection in the common ancestor of a species, they are often restricted to a particular evolutionary clade. While rewiring by TEs can harm a host genome, some of the features of TE invasions can increase host fitness and appear to be universally exploited by various organisms. For instance, TE insertions happen faster than protein-coding genes evolve. They can therefore be coopted for a species-specific evolutionary remodeling of transcriptional networks. Specifically, the LTR12/ERV9 TE family has colonized primate genomes over the past 30 million years and has been widely reported to contribute regulatory elements to the human genome. In this work, we set out to establish the features that made this family successful, and to assess the prevalence of LTR12-derived regulatory elements in early development. We observe the hominoid-restricted LTR12C subfamily to be a driver of transcription in both gametogenesis and early embryogenesis. LTR12C loci have rewired genes involved in ciliogenesis and flagellogenesis that are critical for male fertility. Relatedly, they also present unusual behavior during the epigenetic reprogramming characteristic of these periods by resisting genome-wide demethylation in primordial germ cell (PGC) development. To identify the determinants of the epigenetic status of LTR12C elements that made them attractive for cooption, we turn to KRAB zinc finger proteins (KZFPs). TEs appear to be prominent targets of this large family of epigenetic repressors. Through functional studies, we determine ZNF676 is a regulator of LTR12C, with its targets resisting genome-wide demethylation. This resistance possibly pre-marks them for zygotic rather than maternal expression. We show that ZNF676 levels influence the expression of some cilium-related genes and are able to disrupt ciliogenesis. We conclude this KZFP likely coevolved with its target ERVs, which carried its binding sites into the vicinity of multiple genes, including those important for male fertility. KZFPs can therefore become regulators of genes with a common function along with the transposable elements they target. More generally, in our study of TEs expressed in human embryonic development, we find the expression of some TE families to be a hallmark of a particular development stage, an indicator of the current chromatin state. These markers provide a criterion that can be used to assess the similarity of embryonic development models to real embryos. Transcription of some marker TEs anticorrelates with that of their putative KZFP regulators, implying proper KZFP expression to be important to properly recapitulate embryonic development. Our results provide insight into the TE- and KZFP-mediated rewiring of transcriptional networks related to the germline and early development, and suggest that the improper expression of a KZFP can have consequences ranging up to infertility.

EPFL2021

KRAB zinc finger protein-mediated control of transposon-embedded regulatory sequences from human germline to early embryos

Alexandra Iouranova

EPFL2021