Chromatin Architecture

Abstract

In the nucleus chromosomes are arranged in territories, which are stabilized by a nucleoskeleton formed by lamin filaments. Transcriptionally active chromatin domains are located in the nuclear interior, whereas silent domains reside at the nuclear periphery. Global changes in gene expression correlate with spatial chromatin reorganizations, which play a significant role in lineage restriction during development. Therefore, transcriptionally active genes contribute to the cell type-specific nuclear architecture in differentiated tissues. Moreover, co-regulated genes often cluster at the same chromosomal regions, i.e. groups of genes of similar function are drawn to particular sites within the three-dimensional structure of the nucleus.

In the interchromatin compartment of the nucleus there are subnuclear structures, such as transcription factories, that contain high concentrations of Pol II. Transcription factories function as some sort of a “magnet” for commonly regulated genes with shared nuclear positions. This suggests that the transcriptional status of a gene is based on its position in the nucleus sphere. This transcription factory model has important implications for the regulation of transcription initiation and elongation, for the organization of genes in the genome, for the co-regulation of genes and for genome instability.

In this chapter, we will discuss the impact of the three-dimensional organization of chromatin in the nucleus for the regulation of gene expression. We will learn that the transcription factory model provides a new perspective on a number of phenomena in gene regulation.