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Epigenetic regulation of gene expression in melanoma

Research unit

UMR 7104 - Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC)
1 rue Laurent Fries 67404 ILLKIRCH

Group

Name: Regulation de l'expression génique et cancer

Group leader: DAVIDSON Irwin - irwin@igbmc.fr

Group leader's phone: 0388653445

Group organization:
- Chercheurs: 3
- ITA: 2
- Doctorants: 2
- Post-Docs: 4
- Autres: 0

Publications of the team linked to the topic (3 last years):
1) Herquel B, Ouararhni K, Martianov I, Le Gras S, Ye T, Keime C, Lerouge T, Jost B, Cammas F, Losson R, and Davidson, I. (2013). Trim24 repressed VL30 retrotransposons regulate gene expression by producing noncoding RNA.. Nat. Struc. Mol. Biol. Mar;20(3):339-46. doi: 10.1038/nsmb.2496. Epub 2013 Feb 3..
2) Alpern, D, Langer, D, Ballester, B, Le Gras, S, Romier, C, Mengus, G, and Davidson, I. (2014). TFIID subunit TAF4 directs promoter occupancy of nuclear receptor HNF4A during post-natal hepatocyte differentiation. ELife, Sep 10;3. doi: 10.7554/eLife.03613.
3) Ennen M, Keime C, Kobi D, Mengus G, Lipsker D, Thibault-Carpentier C, and Davidson I. (2014). Single-cell gene expression signatures reveal melanoma cell heterogeneity. Oncogene. Aug 18;0. [Epub ahead of print].

About PhD

PhD Director: DAVIDSON Irwin - irwin@igbmc.fr

Phone: 0388653445

Junior advisor: non

Co-tutely: non

Co-Director: non

About PhD topic :

Title: Epigenetic regulation of gene expression in melanoma

Project: Melanoma is a highly aggressive human cancer. MITF (Microphthalmia-associated transcription factor), a bHLH-bZIP familly transcription factor is a master regulator of the physiology of melanoma cells and melanocytes. MITF controls the proliferation and invasion of melanoma cells. To better understand how MITF regulates transcription we have identified several new MITF cofactors, amongst which are the chromatin remodelling complexes PBAF and NURF. We have used integrative functional and genomics approaches in cellulo and genetics in the mouse to define the critical roles of the PBAF subunit BRG1 and the NURF subunit BPTF in melanoma cells and in the melanocyte lineage. The objective of the project will be to better determine the functions of these remodelling complexes in gene regulation in melanoma in vitro and in vivo. Using melanoma cells, we will investigate the role of each subunit of the PBAF and NURF complexes in control of gene expression, complex integrity and genomic localisation combining knockdown experiments with RNA-seq and ChIP-seq. We have generated recombinant mice with floxed alleles of the genes encoding Brg1 and Bptf such that we can inactive these proteins in a mouse melanoma model. This will allow us to address the role of these proteins in tumourigenesis in vivo. We are also generating a new recombinant mouse expressing a mutated version of the PBAF subunit Arid2 that is found in human melanoma. We will test whether the mutated Arid2 is capable of transforming melanocytes and forming melanoma alone or in combination with oncogenic Braf.

Wished skills: General education in molecular biology and biochemistry.

Expertises which will be acquired during the training: All basic cell culture and molecular biology techniques. Generation, management, physiolopathology and molecular analyses of recombinant mice. Generation, management and bioinformatics analyses of high throughput genomics data.