Luca Giorgetti
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Apr 13, 2022 Enhancer-promoter interactions — distance matters |
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Apr 19, 2021 The architect of genome folding |
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Jun 10, 2019 New method reveals principles of chromatin folding in vivo |
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Luca Giorgetti
Chromosome structure and transcriptional regulation
To establish and maintain gene expression, cells require precise control of transcription. In mammals, this involves trans-acting factors, such as transcription factors binding to promoter-proximal regulatory sequences, as well as cis-acting elements such as cell-type specific enhancers, which are often located hundreds of kilobases away from their target promoters.
Functional interactions between distal enhancers and target promoters require them to be in close physical proximity, which in turn is linked to the way chromosomes fold in the three-dimensional space of the cell nucleus. To fully understand transcriptional regulation, it is therefore fundamental to quantitatively characterize chromosome conformation, including its cell-to-cell and temporal variability.
Chromosome conformation capture (3C)-based studies, which measure chromosomal contacts using chemical cross-linking, have revealed that mammalian chromosomes are partitioned into a complex hierarchy of interaction domains, at the heart of which lie topologically associating domains (TADs) and their substructures. Genetic evidence has shown that these specific chromosomal structures restrict the genomic range of enhancer-promoter communication, as well as fine-tune the three-dimensional interactions between regulatory sequences.
However, the mechanistic details of how physical interactions within chromosomes translate into transcriptional outputs are totally unknown. In our lab, we explore the biophysical mechanisms that link chromosome conformation and long-range transcriptional regulation in mouse embryonic stem cells (ESC) and differentiated derivatives, using molecular biology, genetic engineering, single-cell experiments and physical modelling .
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Luca Giorgetti
This is a list of selected publications from this group. For a full list of publications, please visit our Publications page and search by group name.
Zuin J, Roth G, Zhan Y, Cramard J, Redolfi J, Piskadlo E, Mach P, Kryzhanovska M, Tihanyi G, Kohler H, Eder M, Leemans C, van Steensel B, Meister P, Smallwood S, Giorgetti L (2022) Nonlinear control of transcription through enhancer-promoter interactions
Nature 604, 571-577Mach P, Kos PI, Zhan Y, Cramard J, Gaudin S, Tünnermann J, Marchi E, Eglinger J, Zuin J, Kryzhanovska M, Smallwood S, Gelman L, Roth G, Nora EP, Tiana G, Giorgetti L (2022) Live-cell imaging and physical modeling reveal control of chromosome folding dynamics by cohesin and CTCF
bioRxivZenk F, Zhan Y, Kos P, Löser E, Atinbayeva N, Schächtle M, Tiana G, Giorgetti L, Iovino N (2021) HP1 drives de novo 3D genome reorganization in early Drosophila embryos.
Nature. 2021 Apr 14McCord RP, Kaplan N, Giorgetti L. (2020) Chromosome Conformation Capture and Beyond: Toward an Integrative View of Chromosome Structure and Function
Molecular Cell 77, 688-708Redolfi J*, Zhan Y*, Valdes-Quezada C*, Kryzhanovska M, Guerreiro I, Iesmantavicius V, Pollex T, Grand RS, Mulugeta E, Kind J, Tiana G, Smallwood SA, de Laat W, Giorgetti L (2019) DamC reveals principles of chromatin folding in vivo without crosslinking and ligation
Nature Structural & Molecular Biology 26, 471-480 (2019)Marti-Renom M, Almouzni G,Bickmore W, Bystricky K, Cavalli G, Fraser P, Gasser SM, Giorgetti L, Heard E, Nicodemi M, Nollmann M, Orozco M, Pombo A, Torres-Padilla ME (2018) Challenges and guidelines toward 4D nucleome data and model standards
Nature Genetics 50, 1352-1358Tiana G, Giorgetti L (2018) Integrating experiment, theory and simulation to determine the structure and dynamics of mammalian chromosomes
Curr Opin Struct Biol.49:11-17Zhan Y, Mariani L, Barozzi I, Schulz EG, Bluthgen N, Stadler M, Tiana G, Giorgetti L. (2017) Reciprocal insulation analysis of Hi-C data shows that TADs represent a functionally but not structurally privileged scale in the hierarchical folding of chromosomes
Genome Res. doi: 10.1101/gr.212803.116, [Epub ahead of print]Giorgetti L, Heard E (2016) Closing the loop: 3C versus DNA FISH
Genome Biol, 17:215Zhan Y, Giorgetti L, Tiana G (2016) Looping probability of random heteropolymers helps to understand the scaling properties of biopolymers
Phys Rev E 94:032402Giorgetti L, Lajoie BR, Carter AC, Attia M, Zhan Y, Xu J, Chen CJ, Kaplan N, Chang HY, Heard E, Dekker J (2016) Structural organization of the inactive X chromosome in the mouse
Nature, 535:575-579Tiana G, Amitai A, Pollex T, Piolot T, Holcman D, Heard E, Giorgetti L (2016) Structural fluctuations of the chromatin fiber within topologically associating domains
Biophys J. 110:1234-1245Giorgetti L, Galupa R, Nora EP, Piolot T, Lam F, Dekker J, Tiana G, Heard E (2014) Predictive polymer modeling reveals coupled fluctuations in chromosome conformation and transcription
Cell 157:950-63Nora EP, Lajoye B, Schulz E, Giorgetti L, Okamoto I, Servant N, Piolot T, van Berkum NL, Meisig J, Sedat J, Gribnau J, Barillot E, Blüthgen N, Dekker J, Heard E (2012) Spatial partitioning of the regulatory landscape of the X-inactivation centre
Nature 485:381-5Giorgetti L, Siggers T, Tiana G, Caprara G, Notarbartolo S, Corona T, Pasparakis M, Milani P, Bulyk ML, Natoli G (2010) Noncooperative interactions between transcription factors and clustered DNA binding sites enable graded transcriptional responses to environmental inputs.
Mol Cell 37:418-28Comment in Nat Rev Genetics 11:240
Giorgetti L, Viverit L, Gori G, Barranco F, Vigezzi E, Broglia RA (2005) Quasi-particle properties of trapped Fermi gases
Journal of Physics B 38:949Full list of publications
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