Studying fundamental aspects of gene regulation and molecular network organization: systematic identification of regulatory elements in physiological conditions and development of dedicated bioinformatics approaches and tools
This research axis focus on :
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Deciphering the functional landscape of the coding genome
RNA BIndiNG PrOtein - RNA network
Novel high throughput methods recently led to the discovery of an unprecedented number of proteins able to bind RNAs and reciprocally, thereby revealing a terra incognita of possible regulatory roles. By coupling predictions of RNA-protein interactions and statistical analyses, we recently showed that the scaffolding of protein complex is a prevalent function of long non-coding RNAs (collaboration with G.G. Tartaglia, CRG, Barcelona, Spain and I. Bozzoni, La Sapienza, Rome, Italy). |
Protein-protein interaction (PPI) variant networks
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Deciphering the functional organization of the genome
Enhancers /silencers
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Regulatory variants
Our better understanding of regulatory region and large amount of available data allow us to systematically study the influence of regulatory variation on complex phenotypes. Based on the strengths of the laboratory (Genome-wide association studies, analysis of regulatory regions), we are working on new bioinformatics and experimental methods to understand and predict regulatory variants. On the one hand, we are integrating phenotypic variant information with chromatin and sequence data to gain insights into the molecular properties of functional regulatory variants. We use this knowledge to develop predictive in silico models. On the other hand, we are implementing high-throughput reporter assays in order to test thousands of regulatory variants in parallel. Complex diseases are largely influenced by genomic variants. Therefore, a number of complex diseases are studied in the thematics Axis 2 from the point of view of functional variants (Malaria, Sepsis). The bioinformatics and experimental tools developed here will be thus be shared and tested in collaboration with these laboratory members. |
Chromatin organization and replication
We have previously shown that the replication origins can be grouped into different classes with distinct organization, chromatin environment, and sequence motifs. The current challenge is to specifically dissect the replications origins located in regulatory regions (enhancers, promoters) and address how those initiation sites are replicated with regards to gene expression,regulation and cell differentiation (in collaboration with M. Mechali, IGH, Montpellier). We also pursue our collaboration with S. Khochbin and S. Rousseaux (Institut Albert Bonniot, Grenoble, France) on the molecular basis of male germ cells genome programming, to describe precisely the chromatin remodeling event taking place through spermiogenesis (funded by FRM). Our mid-term objective is to integrate our in-house data with public data encompassing MNase-Seq, RNA-Seq, whole-genome bisulfite sequencing (WGBS), ChIP-Seq from various histone marks and bromo-domain proteins to define precisely the molecular bases of male germ cell genome packaging. |
Deciphering the functional role of non-coding transcripts (eRNA, LncRNA)
enhancer RNA-RBP
In the light of recent findings (ReMap catalogue), we will address the functional role of a specific group of enhancers, the transcribed enhancers. Since some ‘active’ enhancers are transcribed bidirectionally and produce short capped RNA called eRNA, we will investigate their functional role notably by analyzing their propensity to bind RNA Binding Protein (RBPs). |
Long non-coding RNA
Based on in-house RNA-seq data obtained from normal thymocytes and leukemic cells, we will identify lncRNAs dysregulated in leukemia and perform functional assays to study their potential implications in oncogenesis (in collaboration with V. Asnafi, Necker Hospital, Paris, France; funded by ITMO-Plan Cancer). We will also prioritise potentially relevant lncRNAs based on epigenomics profiles we have obtained within the Blueprint consortium. In addition, the prevalence of the role of lncRNAs as scaffolding molecule of protein complexes has been investigated using an original bioinformatic approach coupling predictions of RNA-protein interactions (in collaboration with G.G. Tartaglia, CRG, Barcelona, Spain) and protein-protein interaction network analyses (funded by A*MIDEX grant). |
Deciphering genetic networks in a model organism
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Databases
REMAP
ReMap (remap.cisreg.eu) is an integrative analysis of transcriptional regulators ChIP-seq experiments from both “Public” (GEO / ArrayExpress) and Encode datasets. The ReMap atlas consists of 80 million peaks from 485 transcription factors (TFs), transcription coactivators (TCAs) and chromatin-remodeling factors (CRFs). The ReMap atlas is available to browse or download either for a given TF or cell line, or for the entire dataset. |
MoonDB
MoonDB is a database of Extreme Multifunctional proteins (EMFs) that we recently identified as proteins involved in very dissimilar functions from PPI networks. In addition to functional informations on the 430 identified EMFs, a dataset of 38 literature curated proteins is provided. |