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Project description

The Bonev lab studies how 3D genome organization and epigenetic modifcations regulate cell identity during brain development. Using highly interdisciplinary approaches including single cell multi-omics, mouse genetics and computational biology, we aim to understand how chromatin landscape influences cell fate choices in the cortex. We have previously discovered that regulating 3D chromatin architecture and enhancer-promoter interactions plays an important role in the control of gene expression and cell fate in the cortex. Furthermore, several key transcription factors are associated at the molecular level with dynamic chromatin loops and may function by remodelling genome topology. The goal of this project will be to examine mechanistically how neural transcription factors can dynamically rewire 3D chromatin interactions. It will involve state-of-the art technologies such as CRISPR-Cas9 genome engineering, embryonic stem cells, and NGS techniques such as Hi-C, ATACseq and RNAseq.

Related literature:

Bonev B., et al. (2017), Multiscale 3D genome rewiring during mouse neural development. Cell 171, 557.e1–557.e24.    

Bonev B. & Cavalli G. (2011), Organization and function of the 3D genome. Nature Reviews Genetics 17, 661–678

Bonev B., Pisco A. & Papalopulu, N. (2011), MicroRNA-9 Reveals Regional Diversity of Neural Progenitors along the Anterior-Posterior Axis. Developmental. Cell 20, 19-32.

Deng W, et al. (2012),  Controlling long-range genomic interactions at a native locus by targeted tethering of a looping factor. Cell 149(6) 1233-1244.

Stadhouders R, et al. (2018), Transcription factors orchestrate dynamic interplay between genome topology and gene regulation during cell reprogramming. Nature Genetics 50(2) 238-249.

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