Diffusion Based Looping of Chromatin

Abstract

Chromatin folding inside the interphase nucleus of eukaryotic cells is done on multiple scales of length and time. Despite recent progress in understanding the folding motifs of chromatin, the higher-order folding still remains elusive. Flourescent in situ hybridization reveals a tight connection between genome folding and function as well as a folding into a confined sub-space of the nucleus. The folding state of chromatin reveals distinct differences from a compact conformation. A previously published model, the random loop (RL) model, explains the folding state by the formation of random loops, which themselves seem to be an ubiquitous motif of transcriptional regulation. However, it remains a crucial question what mechanisms are necessary to make two chromatin regions become co-located, i.e. have them in spatial proximity. The model presented here bridges the gap between statistical polymer models and an effective description of the dynamic process of loop formation mediated by the nuclear environment. Without assuming long-range forces or any active transport mechanisms, this model assumes that the formation of contacts or loops is done solely on the basis of random collisions. The probabilistic nature of the formation of temporary contacts mimics the effect of e.g. transcription factors in the solvent. Although only basic interactions are taken into account, this model is in agreement with recent experimental data.