Lamina and Heterochromatin Direct Chromosome Organisation in Senescence and Progeria

BioRxiv : the Preprint Server for Biology
Michael ChiangTamir Chandra

Abstract

Lamina-associated domains (LADs) cover a large part of the human genome and are thought to play a major role in shaping the nuclear architectural landscape. Here, we use simulations based on concepts from polymer physics to dissect the roles played by heterochromatin- and lamina-mediated interactions in nuclear organisation. Our model explains the conventional organisation of heterochromatin and euchromatin in growing cells, as well as the pathological organisation found in oncogene-induced senescence and progeria. We show that the experimentally observed changes in the locality of contacts in senescent and progeroid cells can be explained naturally as arising due to phase transitions in the system. Our model predicts that LADs are highly stochastic, and that, once established, the senescent phenotype should be metastable even if lamina-mediated interactions were reinstated. Overall, our simulations uncover a universal physical mechanism that can regulate heterochromatin segregation and LAD formation in a wide range of mammalian nuclei.

Related Concepts

Mental Association
Cell Nucleus
Genome
Polymers
Heterochromatin-specific nonhistone chromosomal protein HP-1
Anterior Descending Branch of Left Coronary Artery
Shapes
Nuclear
Simulation
Landscapes

Related Feeds

BioRxiv & MedRxiv Preprints

BioRxiv and MedRxiv are the preprint servers for biology and health sciences respectively, operated by Cold Spring Harbor Laboratory. Here are the latest preprint articles (which are not peer-reviewed) from BioRxiv and MedRxiv.