Genome Architecture

GENE REGULATION, STEM CELLS AND CANCER

GROUP LEADER:
Guillaume Filion

POSTDOCTORAL FELLOWS:
Heng-Chang Chen, Catalina Romero, Ruggero Cortini

PhD STUDENT:
Marc Corrales

TECHNICIANS:
Arantxa Rosado, Eduard Valera, Lorena Espinar, Manisha Kabi

INTERNSHIP STUDENTS:
Albert Torello, Egor Tiavlovsky (was here in 2017, gone in 2017)

Summary

The long-term goal of our research group is to understand how the architecture of the genome impacts gene expression. We develop our own technologies, combining molecular biology and bioinformatics to study how the genomic context (chromatin, sequence at a large scale, local conformation of the genome) influences gene regulation. This method, called Thousands of Reporters Integrated in Parallel (TRIP) allows us to measure the expression of a reporter inserted at different locations of a target genome. We are also using TRIP in the clinical context of HIV infections. The expression of proviruses depends on the insertion site, as HIV seems to hijack the nearby enhancers. As a consequence, proviruses inserted far from active genes and enhancers are more likely to become latent and reinfect the patients later in their life. In the context of the 4D Genome ERC Synergy project, we use the contextual information of the three-dimensional organization of the genome to understand and predict the search trajectories of transcription factors. With this information at hand, we hope to understand why the same regulatory element behaves differently in different contexts.

Research Projects

  • Develop the TRIP technology
  • Understand latency in HIV
  • Understand the role of genome conformation

Selected Publications

Corrales M, Rosado A, Cortini R, van Arensbergen J, van Steensel B, Filion GJ.
“Clustering of Drosophila housekeeping promoters facilitates their expression.”
Genome Res, 27(7):1153-1161. doi: 10.1101/gr.211433.116. Epub 2017 Apr 18.

Quilez J, Vidal E, Dily FL, Serra F, Cuartero Y, Stadhouders R, Graf T, Marti-Renom MA, Beato M, Filion G.
“Parallel sequencing lives, or what makes large sequencing projects successful.”
Gigascience, 6(11):1-6. doi: 10.1093/gigascience/gix100 (2017).

Ferry L, Fournier A, Tsusaka T, Adelmant G, Shimazu T, Matano S, Kirsh O, Amouroux R, Dohmae N, Suzuki T, Filion GJ, Deng W, de Dieuleveult M, Fritsch L, Kudithipudi S, Jeltsch A, Leonhardt H, Hajkova P, Marto JA, Arita K, Shinkai Y, Defossez PA.
“Methylation of DNA Ligase 1 by G9a/GLP Recruits UHRF1 to Replicating DNA and Regulates DNA Methylation.”
Mol Cell, 67(4):550-565.e5. doi: 10.1016/j.molcel.2017.07.012. Epub 2017 Aug 10.

Serra F, Baù D, Goodstadt M, Castillo D, Filion GJ, Marti-Renom MA.
“Automatic analysis and 3D-modelling of Hi-C data using TADbit reveals structural features of the fly chromatin colors.”
PLoS Comput Biol, 13(7):e1005665. doi: 10.1371/journal.pcbi.1005665. eCollection 2017 Jul.