Stage Master

Binding of sequence-specific transcription factors (TFs) to DNA regulates transcriptional gene expression. In addition, epigenetic marks characterize regions with distinct regulatory functions. For example, DNA methylation is thought to repress the physical access of transcription factors to DNA. We have recently shown that binding of the TF NRF1 is indeed repressed by DNA methylation genome-wide and that it relies on other transcription factors to create a hypomethylated motif (Domcke/Bardet et al. Nature 2015).

During this internship, you will investigate the dynamics of NRF1 binding in different cell types. Using DNase hypersensitivity profiling and TF sequence motifs, you will infer NRF1 binding across mouse and human cell types. You will use matching profiles of DNA methylation to validate its sensitivity to DNA methylation. Finally, you will explore the cooperativity of NRF1 with other TFs to better understand the features of NRF1 binding.

Throughout this work, you will integrate a large variety of published sequencing datasets (ChIP-seq, DNase-seq, Bis-seq, RNA-seq) across cell types and species and using a machine learning approach combine them to the underlying sequence information (e.g. TF motifs, sequence composition) to identify features of TF binding.

Skills:
- Bioinformatics background with experience working in a linux environment
- Good level in a scripting language (e.g. bash, python, perl) and R as well as data analysis techniques and statistics
- Previous experience working with NGS datasets is a plus
- Good knowledge of biology and interest in genomics and gene regulation
- Ability to work in a team with both experimental and computational biologists
- Good level in spoken and written english

This internship can be extended to a PhD project.

Contact: Anaïs Bardet, CR2 CNRS
Please send a cover letter, CV and grades and ranking to This email address is being protected from spambots. You need JavaScript enabled to view it.
Do not hesitate to contact us for more details

Laboratory: Michaël Weber - Epigenetic regulation of cell identity - UMR 7242
http://irebs.cnrs.fr/spip.php?rubrique186

References
- Domcke S*, Bardet AF*, Ginno P, Hartl D, Burger L, Schübeler D. Competition between DNA methylation and transcription factors determines binding of NRF1. Nature (2015) 528(7583):575-9
- Bardet AF*, Steinmann J*, Bafna S, Knoblich JA, Zeitlinger J, Stark A. Identification of transcription factor binding sites from ChIP-seq data at high-resolution. Bioinformatics (2013) 29(21):2705-13
- Bardet AF, He Q, Zeitlinger J, Stark A. A computational pipeline for comparative ChIP-seq analyses. Nature Protocols (2012) 7(1):45-61
- He Q*, Bardet AF*, Patton B, Purvis J, Johnston J, Paulson A, Gogol M, Stark A, Zeitlinger J. High conservation of transcription factor binding and evidence for combinatorial regulation across six Drosophila species. Nature Genetics (2011) 43(5):414-20