Group News

Jul 4, 2023
Luca Giorgetti elected as EMBO Member

Feb 8, 2023
Luca Giorgetti receives SNSF Consolidator Grant

Dec 5, 2022
Video: Mighty proteins keep DNA regions close for longer

Apr 13, 2022
Enhancer-promoter interactions — distance matters

Apr 19, 2021
The architect of genome folding

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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, 571-577

Mach 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) Cohesin and CTCF control the dynamics of chromosome folding

Nat Genet. 2022 Dec;54(12):1907-1918

Zenk 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 14

McCord RP, Kaplan N, Giorgetti L. (2020) Chromosome Conformation Capture and Beyond: Toward an Integrative View of Chromosome Structure and Function

Molecular Cell 77, 688-708

Redolfi 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, 1352-1358

Tiana G, Giorgetti L (2018) Integrating experiment, theory and simulation to determine the structure and dynamics of mammalian chromosomes

Curr Opin Struct Biol.49:11-17

Zhan 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, 17:215

Zhan Y, Giorgetti L, Tiana G (2016) Looping probability of random heteropolymers helps to understand the scaling properties of biopolymers

Phys Rev E 94:032402

Giorgetti 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, 535:575-579

Tiana 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. 110:1234-1245

Giorgetti 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 157:950-63

Nora 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 485:381-5

Giorgetti 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 37:418-28
Comment 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 38:949

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