Andrey lab: epigenetic control of developmental processes
Konrad Guenther, Vom Urtier zum Menschen, 1909.
During embryogenesis, the activation and repression of genes in time and in space instruct the fabric of organs and structures. The molecular processes that orchestrate these activities are thus essential for the development of the organism and their perturbations can lead to malformations or diseases. One of such processes is the communication, in the nuclear space, between gene regulatory regions and genes themselves. This communication is propagated through the 3D architecture of the genome, specifically through physical chromatin interactions. In many instances one has observed that these interactions occur in very-well defined cell type or tissue, where the gene is active, while they are absent in others, where the gene is inactive.
High resolution Capture-HiC to characterize the 3D genome
In our laboratory, we are studying the regulatory role of these dynamic chromatin interactions in establishing the tightly regulated expression patterns of development genes. To do so, we are using a combination of engineered mouse transgenic lines and high-resolution mapping of chromatin interactions and epigenetic alterations. Moreover, we aim at manipulating the regulatory 3D architecture and epigenomic landscapes of developmental genes in vivo. Ultimately, our goal is to establish the rules that govern the relationship between 3D genome architecture, gene expression and normal/abnormal embryonic development.
Changes in 3D genome conformation can induce ectopic gene expression and lead to leg malformations (Adapted from Kragesteen et al., Nat Genet., 2018)
Preformed Chromatin Topology Assists Transcriptional Robustness of Shh during Limb Development.
Proc Natl Acad Sci U S A. 2019 May 30. pii: 201900672. doi: 10.1073/pnas.1900672116
Dynamic 3D chromatin architecture contributes to enhancer specificity and limb morphogenesis.
Kragesteen BK, Spielmann M, Paliou C, Heinrich V, Schöpflin R, Esposito A, Annunziatella C, Bianco S, Chiariello AM, Jerković I, Harabula I, Guckelberger P, Pechstein M, Wittler L, Chan WL, Franke M, Lupiáñez DG, Kraft K, Timmermann B, Vingron M, Visel A, Nicodemi M, Mundlos S, Andrey G.
Nat Genet. 2018 Oct;50(10):1463-1473. doi: 10.1038/s41588-018-0221-x. Epub 2018 Sep 27.
Characterization of hundreds of regulatory landscapes in developing limbs reveals two regimes of chromatin folding.
Andrey G, Schöpflin R, Jerković I, Heinrich V, Ibrahim DM, Paliou C, Hochradel M, Timmermann B, Haas S, Vingron M, Mundlos S.
Genome Res. 2017 Feb;27(2):223-233. doi: 10.1101/gr.213066.116. Epub 2016 Dec 6.
Formation of new chromatin domains determines pathogenicity of genomic duplications.
Franke M, Ibrahim DM, Andrey G, Schwarzer W, Heinrich V, Schöpflin R, Kraft K, Kempfer R, Jerković I, Chan WL, Spielmann M, Timmermann B, Wittler L, Kurth I, Cambiaso P, Zuffardi O, Houge G, Lambie L, Brancati F, Pombo A, Vingron M, Spitz F, Mundlos S.
Nature. 2016 Oct 13;538(7624):265-269. doi: 10.1038/nature19800. Epub 2016 Oct 5.
Deletions, Inversions, Duplications: Engineering of Structural Variants using CRISPR/Cas in Mice.
Kraft K, Geuer S, Will AJ, Chan WL, Paliou C, Borschiwer M, Harabula I, Wittler L, Franke M, Ibrahim DM, Kragesteen BK, Spielmann M, Mundlos S, Lupiáñez DG, Andrey G.
Cell Rep. 2015 Feb 4. pii: S2211-1247(15)00029-7. doi: 10.1016/j.celrep.2015.01.016.
A switch between topological domains underlies HoxD genes collinearity in mouse limbs.
Andrey G, Montavon T, Mascrez B, Gonzalez F, Noordermeer D, Leleu M, Trono D, Spitz F, Duboule D.
Science. 2013 Jun 7;340(6137):1234167. doi: 10.1126/science.1234167.