Leonid Mirny (MIT)
Chromatin as a memory machine
One of the hallmarks of nuclear organization in eukaryotes is the spatial segregation of transcriptionally active (euchromatin) and inactive (heterochromatin) genomic regions. Recently we found that such compartmentalization is driven by affinity between heterochromatin regions (Falk et al Nature 2019) . Despite the widespread of such compartmentalized organization in nature, its functional roles remain elusive.
Here we examine the role of compartmentalization in the maintenance of epigenetic memory, i.e. maintenance of pattern of histone marks for hundreds of generations. We modeled joint dynamics of chromatin and histone marks: loss and spreading of marks, and refolding of chromosomes through the cell cycle. A surprinting analogy between the spreading of histone marks and the spreading of a disease in a pandemic helped to identify factors that provide robust memory. We further found a parallel between epigenetic memory and an associative memory in the neural network. Our analysis shows that operation of chromatin as a memory device requires enzyme limitation and spatial spreading of the marks in the dense and spatial segregated heterochromatin, suggesting a functional role for this hallmark of nuclear organization.
En version hybride, dans la salle de séminaire du LPTMC (couloir 13-12, 5ème, salle 5-23) et sur zoom: