About Tina
Read about Tina’s project.
Supervision
Genevieve Almouzni
Institut Curie, 1st Supervisor
Stefan Mundlos
MPIMG, 2nd Supervisor
Objectives
Understand how histone H3 variants organise in the genome and in space throughout the cell cycle, to define chromosome and nuclear territories. Histones H3 variants are closely related in terms of sequence, yet they are handled by distinct chaperones that channel them into specific deposition pathways during the cell cycle. As a result, nucleosomes containing particular H3 variants segregate in the genome into different territories. How their genomic distribution impacts chromosome folding, spatial segregation of nuclear territories and ultimately chromatin function have remained open questions.
Methodology
To gain understanding into the importance of H3 variants and relevant chaperones in chromosome architecture and function, the ESR will:
• Compare epigenomic maps of the variants to Hi-C contact maps, to define whether a co-segregation of particular variants occurs with topological domains.
• Compare Hi-C maps to the spatial distribution of variants at specific sites in high resolution
• Evaluate the role of selected histone chaperones in guiding the genomic distribution of variants at specific sites, and their impact on nuclear organisation. The experimental approaches used will be:
1. ChIP-seq to map specific histone variants in model human and mouse cell lines.
2. Bioinformatics to compare their enrichment related to Hi-C contact maps.
3. Imaging of specific chromatin territories with FISH/merFISH and histone variants in super-resolution microscopy (STORM)
4. Modelling approaches to understand their spatial distribution related to chromosome territories.
5. CRISPR/Cas9 and degron strategies to perturb selected chaperones.
Expected Results
Improved understanding of the spatial organisation of chromatin domains defined by histone variants. Identifying the role of particular histone chaperones as a flexible network ensuring this organisation and its plasticity.
Planned Secondments
CNAG-CRG, Spain (2x 1 month):
Hi-C analysis and comparison to ChIP-seq data.
FUNDACIÓ PRIVADA D’ESTUDIS I RECERCA ONCOLÒGICA – FERO, Spain (2 weeks):
Learning about fundraising and research evaluation process.
Enrolment in doctoral programs
PhD in Biology from University Pierre and Marie Curie and Paris Sciences Lettre University (Life Complexity School). Institut Curie (IC) – Paris Sciences Lettres (PSL)
References
Clement, C. et al. High-resolution visualization of H3 variants during replication reveals their controlled recycling. Nat Commun 9, 3181, doi:10.1038/s41467-018-05697-1 (2018).
Yadav, T., Quivy, J. P. & Almouzni, G. Chromatin plasticity: A versatile landscape that underlies cell fate and identity. Science 361, 1332-1336, doi:10.1126/science.aat8950 (2018).