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 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 .

Additional information
FMI report pages for Luca Giorgetti

Luca Giorgetti
Isabella Bogdal
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