Jun 10, 2019
New method reveals principles of chromatin folding in vivo
Sep 6, 2017
Three FMI group leaders awarded prestigious European Research Council Grant
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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 how chromosomes fold int 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 .
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.
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 ligationNature 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 standardsNature Genetics 50, 1352-1358
Tiana G, Giorgetti L (2018) Integrating experiment, theory and simulation to determine the structure and dynamics of mammalian chromosomesCurr 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 chromosomesGenome Res. doi: 10.1101/gr.212803.116, [Epub ahead of print]
Giorgetti L, Heard E (2016) Closing the loop: 3C versus DNA FISHGenome Biol, 17:215
Zhan Y, Giorgetti L, Tiana G (2016) Looping probability of random heteropolymers helps to understand the scaling properties of biopolymersPhys 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 mouseNature, 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 domainsBiophys 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 transcriptionCell 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 centreNature 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 gasesJournal of Physics B 38:949
Full list of publications
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