Research Projects

Chromatin topology studies in mouse ES and human leukemia cell lines

Diagenode

Liege

Belgium

13/13

Supervision

Celine Sabatel
Diagenode, 1st Supervisor

Maria Elena Torres-Padilla
HMGU, 2nd Supervisor

Objectives

Understand how changes in chromatin topology occur during cell differentiation with HT technologies. The organization of the nuclear chromatin is extremely relevant to the biological function at the gene level and at the global nuclear level.
ESR13 will investigate how the spatial organization of chromatin affects gene regulation and differentiation. Firstly developing an optimized Hi-C kit to study chromatin interacting domains in mouse embryonic pluripotent and differentiated stem cells to identify which interacting domains are involved in cell differentiation.
As proof of concept, ESR13 will use the results obtained using ESCs. They will be fully differentiated into cardiomyocytes and compared with the functional and genome-wide analysis data published by the coordinator, L. Di Croce (P1a). Secondly, ESR13 will study the role of the chromatin in genome regulation in normal conditions and in disease by using Hi-C technology to study chromatin topological associated domains (TADs) in leukaemia and differentiated induced leukaemia cell lines.

Methodology

Chipmentation for Chromatin Immunoprecipitation sequencing in low cell number. Hi-C analysis. FISH. RNA-seq. ATAC-seq.

Expected Results

Identification of chromatin interacting domains affecting cell differentiation. Development of a Hi-C kit.

Planned Secondments

CRG, Spain (1 month):
Hi-C data analyses and functional comparison and functional analyses.
Characterisation of interacting domains in differentiated induced leukaemia cells.
UCPH, Denmark (3 weeks):
Integration of ChIP-seq data and ATAC-seq data in leukemic cell model system.

Enrolment in doctoral programs

PhD in Biochemistry from Universitat Pompeu Fabra

References

Laczik M, Hendrickx J., Veillard A.C., Tammoh M., Marzi S. and Poncelet D. Iterative fragmentation improves the detection of ChIP-seq peaks for inactive histone marks. Bioinformatics and Biology Insights 10:209-224, 2016.

Berguet G, Hendrickx J, Sabatel C, Laczik M, Squazzo S, Mazon Pelaez I, Saxena R, Pendeville H, Poncelet D. Automating ChIP-seq experiments to generate epigenetic profiles on 10,000 HeLa cells. J Vis Exp. 2014; (94): 52150.

Veillard A.C., Datlinger P., Laczik M., Squazzo S. and Bock C. Diagenode® premium RRBS technology: cost-effective DNA methylation mapping with superior coverage. Nature Methods 13:184, 2016.