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Update: 11-08-2017

Epigenetics and Splicing

(Department Genome Dynamics)

 

Leader: Reini FERNANDEZ DE LUCO

 

Alternative splicing is one of the most general and important biological processes in the eukaryotic cell. It affects more than 90% of human genes, it is essential for protein diversity and any misregulation of the highly tissue-specific alternative splicing programs can lead to disease, such as cancer. However the mechanisms of cell-specific alternative splicing regulation are still largely unknown.

Unexpectedly, in the past 15 years, chromatin and epigenetic modifications have been shown to play an important role in the regulation of alternative splicing.
In particular, we have shown that non-coding RNAs and histone marks can talk to the splicing machinery via recruitment of chromatin/splicing-adaptor complexes.

Our group aims at the better understanding of the role of epigenetics and long non-coding RNAs in the onset and maintenance of tissue-specific splicing programs using as a cell redifferentiation model system the epithelial-to-mesenchymal transition (EMT). For that purpose we will use chromatin immunoprecipitation (ChIP) and genome-wide strand-specific RT and ChIP deep-sequencing to depict the molecular mechanisms of regulation of tissue-specific alternative splicing.


(Header artwork from "Miromosome" by Luisa Lente)









 

Keywords: Alternative splicing, epigenetics, non-coding RNA, EMT

 

Group's News

 

Opportunities The role of lncRNAs in the epithelial-to-mesenchymal transition.

The epithelial-to-mesenchymal transition (EMT) is a biological process that plays an essential role in pathways such as embryonic development and wound healing. However, it also plays a pivotal part during tumorigenesis, allowing tumour epithelial cells to lose their polarity and their capacity to form inter-cellular junctions, and in this manner gaining a strong capacity for migration. Carcinoma EMT is one of the first steps leading to metastasis and contributes to a highly unfavourable prognostic, giving the tumour a larger adaptation capacity, including to chemotherapy. Recently, several studies have demonstrated the potential implication of long non-coding RNAs (lncRNAs) in EMT progression. Furthermore, preliminary genome-wide sequencing data obtained in the host lab, have allowed us to identify several lncRNAs which not only change expression during EMT but are also neighbouring genes whose correct expression is essential for this detrimental cellular transition to occur and whose expression are also changing, making these lncRNAs prime candidates in EMT regulation.
Using next-generation sequencing data obtained from cells at various stages of the EMT process, molecular biology techniques and human mammary epithelial cell culture, the goal of the student will be to identify and characterize lncRNAs playing an essential role in the regulation of genes that control the EMT process.

The internship will take place in Reini Luco’s laboratory at the Institute of Human Genetics in Montpellier under the supervision of Andrew Oldfield.

Opportunities POSTDOC POSITION

A postdoctoral position is available at the group of Reini Luco at the Institut de Génétique Humaine in Montpellier, in the South of France.

Luco’s lab works on the role of chromatin and long non-coding RNAs in the regulation of cell-specific alternative splicing (for more details see Gonzalez et al., Nat. Str. Mol. Biol 2015 22(5):370-6 and Luco et al., Science 2010 327(5968):996-1000).

The project aims at identifying novel chromatin regulators involved in the regulation of alternative splicing using as a model system the dynamic and inducible Epithelial-to-Mesenchymal Transition (EMT). By using proteomics, we will identify unsuspected new chromatin regulators that interact with the splicing machinery and test their effect on EMT-specific splicing and EMT progression itself.

We are looking for very motivated, hard-working and creative candidates with strong background in molecular biology. Previous expertise in splicing and/or epigenetics will be positively evaluated.

Please provide a detailed CV with a list of publications and expertise, a letter of motivation and the names and contacts of two referees to Reini Luco, reini.luco@igh.cnrs.fr

News Talents du CNRS - Médailles de bronze 2016

Reini FERNANDEZ DE LUCO, Chargée de Recherche, est lauréate 2016 pour la médaille de Bronze du CNRS.
Cette médaille récompense le premier travail d'un chercheur, qui fait de lui un spécialiste de talent dans son domaine. Cette récompense représente un encouragement du CNRS à poursuivre des recherches bien engagées et déjà fécondes.

News Le Cercle FSER

C'est à Paris que se déroulera le 12 janvier 2016 la cérémonie officielle au cours de laquelle REINI FERNANDEZ DE LUCO recevra, ainsi que deux autres biologistes, le Prix de la fondation Schlumberger pour l'Education et la Recherche (FSER).

Read more

 

The 2 lastest publications of the group:

Luco RF.
Retrotransposons jump into alternative-splicing regulation via a long noncoding RNA
(2016), Nat Struct Mol Biol : 23(11):952-954
Gonzalez I, Munita R, Agirre E, Dittmer TA, Gysling K, Misteli T, Luco RF..
A lncRNA regulates alternative splicing via establishment of a splicing-specific chromatin signature
(2015), Nat Struct Mol Biol : 22, 5, 370-376

 

All the publications of the group

Staff:


Name / First name Room Phone status

   Researcher

FERNANDEZ DE LUCO Reini S10-S11 9912 CR (CNRS) E-mail    Photo  

   Engineer & Administrative

VILLEMIN Jean-Philippe S10-S11 9912 IE (CNRS) E-mail    Photo  

   Post-Doc

OLDFIELD Andrew S10-S11 9912 (CNRS) E-mail    Photo  

   PhD students

SEGELLE Alexandre S10-S11 9912 (Univ.Montp) E-mail    Photo  

Epigenetics and Splicing Group

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  INSTITUTE of HUMAN GENETICS
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  Montpellier, France