We measured individual trajectories of fluorescently labeled telomeres in the nucleus of eukaryotic cells in the time range of 10 À2 -10 4 sec by combining a few acquisition methods. At short times the motion is subdiffusive with hr 2 i $ t and it changes to normal diffusion at longer times. The short times diffusion may be explained by the reptation model and the transient diffusion is consistent with a model of telomeres that are subject to a local binding mechanism with a wide but finite distribution of waiting times. These findings have important biological implications with respect to the genome organization in the nucleus. DOI: 10.1103/PhysRevLett.103.018102 PACS numbers: 87.16.Zg, 05.40.Jc, 87.15.Vv The nucleus of the eukaryotic cell contains tens of thousands of genes ($23 000 in human) organized as chromosomal DNA. This crowded environment contains packed genetic material, RNA transcripts, protein factors, and a variety of nuclear bodies. The genetic information (DNA) can be either replicated to form daughter cells, or transcribed to RNA molecules leading to protein translation. These processes depend on the ability of protein factors to locate and interact with specific DNA sequence within this packed nucleus [1], as well as on the organization and structure of chromatin in the nucleus [2]. Telomeres are the end caps of the linear eukaryotic chromosomes. They play an important role in maintaining chromosome organization and integrity throughout the cell cycle. The telomeres are protected by a number of protein factors that are collectively referred to as shelterin and can bind to either the nuclear envelope, nuclear matrix, or heterochromatin, depending on the cell species [3]. Therefore, studying the dynamics of telomeres can shed light on chromosome dynamics, the role of telomeres in genome organization, and the coordination of physical structures and biological processes in the nucleus [4].Chromosomes occupy specific nuclear volumes referred to as chromosome territories [5], and their motion is highly constrained. The diffusion of telomeres was previously studied on a limited time scale of either minutes [6] or 1-200 sec [7] and exhibited mainly normal constrained diffusion with a heterogeneous diffusion coefficient of 2-6 Â 10 À4 m 2 =s. This is significantly lower than the diffusion of small molecules such as dextran in the nucleus (10-100 m 2 =s), which reflects the dense nature of the nucleus. The dynamics of other nuclear bodies as well as messenger RNAs were also measured [8][9][10] and anomalous diffusion was found for specific DNA loci [11].In this study, we examined the diffusion properties of telomeres in the nucleus in a broad time range of almost 6 orders of magnitude (10 À2 -10 4 sec ). Such a broad time range was employed by combining two different imaging setups on the same microscope. We find that the diffusion is anomalous at short times of $10 À2 -10 3 sec . It changes to normal diffusion at longer time intervals and the diffusion constants are found to have a wide distribution...

Internal organization and dynamics of the eukaryotic nucleus have been at the front of biophysical research in recent years. It is believed that both dynamics and location of chromatin segments are crucial for genetic regulation. Here we study the relative motion between centromeres and telomeres at various distances and at times relevant for genetic activity. Using live-imaging fluorescent microscopy coupled to stochastic analysis of relative trajectories, we find that the interlocus motion is distance-dependent with a varying fractional memory. In addition to short-range constraining, we also observe long-range anisotropic-enhanced parallel diffusion, which contradicts the expectation for classic viscoelastic systems. This motion is linked to uniform expansion and contraction of chromatin in the nucleus, and leads us to define and measure a new (to our knowledge) uniform contraction-expansion diffusion coefficient that enriches the contemporary picture of nuclear behavior. Finally, differences between loci types suggest that different sites along the genome experience distinctive coupling to the nucleoplasm environment at all scales.