Large-scale nuclear architecture and transcriptional control

Abstract

Transcriptional regulation is one the most basic mechanisms for controlling gene expression. Over the past few years, much research has been devoted to understanding the interplay between transcription factors, histone modifications and associated enzymes required to achieve this control. However, it is becoming increasingly apparent that the three-dimensional conformation of chromatin in the interphase nucleus also plays a critical role in regulating transcription. Chromatin localisation in the nucleus is highly organised, and early studies described strong interactions between chromatin and sub-nuclear components. Single-gene studies have shed light on how chromosomal architecture affects gene expression. Lately, this has been complemented by whole-genome studies that have determined the global chromatin conformation of living cells in interphase. These studies have greatly expanded our understanding of nuclear architecture and its interplay with different physiological processes. Despite these advances, however, most of the mechanisms used to impose the three-dimensional chromatin structure remain unknown. Here, we summarise the different levels of chromatin organisation in the nucleus and discuss current efforts into characterising the mechanisms that govern it.