The complex architecture displayed by the chromatin inside the nucleus of eukaryotic cells plays an important role in several key cellular processes such as the regulation of gene expression, DNA replication and DNA repair. The dynamics of this chromatin architecture remains however poorly characterized. While at “steady state” the chromatin organization is thought to be relatively stable along the entire interphase, dramatic modifications of this architecture has been observed in response to external stimuli. In particular, the activation or repression of gene transcription is often associated with local changes in the level of chromatin compaction and with gene repositioning inside the nucleus. A precise understanding of the mechanism underlying this chromatin reorganization is impeded by the lack of a complete description of the dynamics of the restructuring process.
With the “ChromaTranscript” project, the researcher proposes to investigate the process of nuclear restructuring in association to transcriptional activation or repression of estrogen-regulated genes using an original approach at the interface between biology, physics and advanced microscopy. The three following questions will be investigated:
1) What is the dynamic of the nuclear reorganization process at the scale of a single chromosome ?
2) What are the changes in the fine chromatin structure underlying the micron-scale nuclear reorganizations studied in 1) ?
3) Is nuclear reorganization the cause or the consequence of the change in transcription activity ?
The interdisciplinary approach which is proposed in the project combines tagging methods, used to label in fluorescence single chromosome or specific gene loci in living cells, and advanced light microscopy methods allowing the monitoring, at different scales in space and time, of the process of nuclear restructuring in association to transcription modulation.
Fields of science
Call for proposal
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