"Epigenetics: From Structure to Function"

ABSTRACT of the lecture

The organization of the genetic material inside a eukaryotic cell is a packaging wonder. You start unpacking the 5-10 μm wide nucleus and the DNA would stretch up to 2 meters. Such extraordinary level of compaction is achieved with the help of specialized proteins, that unable the DNA to fold into complex structure with multiple coils and loops, which is termed chromatin. This is in this context that DNA templated functions (regulated gene expression, DNA repair, DNA replication, mitosis, etc.) take place and chromatin has to be initially unfolded and then refolded upon completion of the nuclear process in order to preserve nucleus homeostasis. Alterations in the chromatin organization result in perturbations in the nucleus epigenetic landscape and lead to numerous diseases.

We have recently solved the structure of the chromatin filament induced by the binding of the linker histone H1, which after the deciphering the structure of DNA and the nucleosome core particle, remained the main problem in structural epigenetics that has defied the chromatin and epigenetic community for more than 40 years. I will initially present these findings and then I will show how the main epigenetic factor, the histone variant H2A.Z , shape chromatin and preserve nucleus homeostasis.

By using a large cohort of molecular and cell biology, biochemistry and genome-wide epigenetic approaches combined with mouse genetics, including conditional knock-out mice, we have identified an intimate crosstalk between H2A.Z, innate immune response and inflammation. The second part of the talk will be concentrated on these data.

During the last years, our lab was very much interested in the etiology of epigenetic and rare diseases.

At the third part of the talk, some of our data on both Rett syndrome, a very severe

neurodevelopmental disease, and Rahman syndrome, a newly identified rare disease casually linked with mutations in the linker histone H1, will be also presented.

REFERENCES:

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2. Garcia-saez et al., Mol Cell. 2018 Dec 6;72(5):902-915.e7.

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3. Obri, A. et al. Nature. 2014 Jan 30;505(7485):648-53

4. Graies et al., submitted