Chromosome positioning from activity-based segregation
Prof. S. Sengupta (TIFR Centre for Interdisciplinary Sciences, Hyderabad, India)

Chromosomes within eukaryotic cell nuclei at interphase are not positioned at random, since gene-rich chromosomes are predominantly found towards the interior of the cell nucleus across a number of cell types. The physical mechanisms that could drive and maintain the spatial segrega- tion of chromosomes based on gene density are unknown. Here, we identify a mechanism for such segregation, showing that the territorial organiza- tion of chromosomes, another central feature of nuclear organization, emerges naturally from our model. Our computer simulations indicate that gene density-dependent radial segregation of chromosomes arises as a robust consequence of differences in non-equilibrium activity across chromosomes. Arguing that such differences origin- ate in the inhomogeneous distribution of ATP- dependent chromatin remodeling and transcription machinery on each chromosome, we show that a variety of non-random positional distributions emerge through the interplay of such activity, nuclear shape and specific interactions of chromo- somes with the nuclear envelope. Results from our model are in reasonable agreement with experimental data and we make a number of predictions that can be tested in experiments.

Reference: Nirmalendu Ganai, Surajit Sengupta and Gautam I. Menon, Nucleic Acids Research, 2014, 1–15 doi:10.1093/nar/gkt1417