Genetics and cell biology

In vivo chromatin and transcription

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Group Leader

Alessandra Agresti

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Chromatin contains DNA packaged by histones, by associated proteins and RNA. The dynamic structure of chromatin modulates nuclear processes, like transcription and replication, by altering the accessibility of DNA to regulatory factors. This group aims at understanding how chromatin 3D-structure affects nuclear transactions like DNA transcription and replication. 

Research activity

From the chromatin standpoint, this unit recently found that the nuclear amount of histones – and therefore of nucleosomes – is not a fixed parameter, as generally thought, but a tunable one that cells exploit to respond to the evolving environment. Researchers are now investigating how nucleosome occupancy varies in regulatory, coding and intervening sequences in cells responding to inflammatory cues. Molecular rulers governing the nucleosome number are also actively sought.

From a reciprocal standpoint, the prototypic transcription factor NF-kB dynamically browses chromatin and interacts with cognate sites on the timescale of seconds to regulate the transcriptional inflammatory response. On the timescale of hours, NF-kB undergoes cycles of cytoplasmic-to-nuclear and nuclear-to-cytoplasmic translocations, giving rise to ‘‘oscillations’’. In turn, oscillations tune the transcriptional output. The group is now integrating short and long timescale NF-kB dynamics by mathematical modeling and systems biology approaches to a better understanding of transcriptional control in inflammation. In parallel, systems to study transcription at single cell level are being developed.
The role of nucleosome occupancy in DNA replication is also investigated.