Understanding the details of how chromatin folds and the physical parameters governing its behavior are among the most intriguing challenges in modern cell biology. Recent insights on chromosome conformation in yeast nuclei were gained owing to high-throughput molecular biology techniques [1], but the physical parameters governing chromosomes dynamics remain unelucidated. We have recently developed an original fast 3D fluorescence microscopy technique for studying chromatin in living yeast [2], which allows sampling its dynamics with temporal resolutions of 15 ms. We reasoned that this technology could be applied to map the dynamics of a unique combination of 14 loci tagged in chromosome III, IV, VI, XII and XIV at the single cell level in yeast. The spatio-temporal dynamics of these loci, as inferred from their mean square displacement, appeared to be similar over a very large time domain from 10 ms to 50 s. Moreover, anomalous sub-diffusive behaviors were systematically detected, and the anomaly parameters were consistent with the polymer model of reptation that describes polymers as snakes randomly crawling in grass. This model is characterized by distinct dynamics at short and long time scales, Rouse and reptation behaviors, respectively, that were both observed experimentally. The quantitative analysis of our results unravels that two parameters of chromatin, namely its persistence length and its viscous friction, suffice to determine its dynamics. Finally, we are currently analyzing the dynamics of a variety of yeast mutants, in which chromatin structural proteins have been depleted, to explore how chromatin compaction is regulated in vivo and its effect on chromatin dynamics. Taken together, our study sheds new light on chromatin structure and dynamics built on physical models. 1. Duan, Nature, 2010. 2. Hajjoul, Lab on a Chip, 2009.