The three-dimensional organisation of the genome plays a fundamental role in the regulation of gene expression. However, despite the recent characterisation of regulators associated to this organisation, we currently lack an understanding of how chromatin conformation is first established during development, and the molecular mechanisms that drive this process.
In the first part of my talk, I will focus on recent work in which, using Drosophila as a model system, we investigated chromatin conformation dynamics in embryos at different time points during early embryonic development. Using genetic tools and single-cell technologies, we evaluate the level of heterogeneity in chromatin conformation across different tissues at sub-kilobase resolution. This allows us to unveil that the three-dimensional organisation of chromatin at this developmental stage is likely to serve as an architectural framework to enable transcriptional regulation.
In the second part of my talk, I will turn into mammalian early embryonic development. In particular, I will focus on transposable elements, which are highly abundant in eukaryotic genomes and have been recently associated with the process of zygotic genome activation. Using genome-wide chromatin conformation maps, I will show how the Murine Endogenous Retroviral Element (MuERV-L/MERVL) family of transposable elements drives 3D chromatin reorganisation in 2-cell-embryo-like cells as well as in the mouse 2-cell embryo. This reorganisation involves the emergence of hundreds of TAD boundaries across the genome and it is associated to the upregulation of directional transcription from MERVL, which results in the activation of a subset of 2-cell embryo genes. These results have important implications for our understanding of how nuclear organisation emerges during zygotic genome activation in mammals, and how this organisation can be influenced by repetitive elements during early embryonic development.
Juanma (Spanish short form for ‘Juan Manuel’) is MRC Investigator and Programme Leader at the MRC London Institute of Medical Sciences and Imperial College London, UK. He has a long-standing interest in understanding the molecular mechanisms that allow cells to use their genetic information to perform normal cellular and physiological functions, such as development and differentiation, and how the mis-regulation of these mechanisms leads to disease, such as cancer.
Recent highlights from Juanma's group include: i) the first characterisation of the emergence of chromatin conformation in vivo (Hug et al., Cell 2017), and during tissue-specification (Ing-Simmons et al., Nat Genet 2021); ii) the development of a low-input Hi-C protocol that can be used for clinical purposes (Díaz, Kruse et al., Nat Commun 2018); and, iii) the development of analytical tools for the analysis and integration of genomics data (Galan et al., Nat Genet 2020; Kruse et al., Genome Biol 2020).