Chromatin Remodeling

Abstract

The regulation of gene expression comprises a dynamic balance between packing genomic transcription factor binding sites into inaccessible chromatin and allowing proteins to access these sequences. This is controlled by histone modifications (see Chap. 8), DNA methylation (see Chaps. 9 and 10) and ATP-dependent chromatin remodeling. Chromatin remodeling factors are multi-protein complexes that use the energy of ATP hydrolysis, in order to remodel or remove nucleosomes regulating the exposure of genomic DNA to transcription factors.

Genome-wide studies suggested important concepts for the regulation of open and closed promoters. Closed promoters are “poised” in their repressed state being characterized by nucleosome positioning and depletion, histone modifications and variants as well as the presence of stalled Pol II. Chromatin modification and remodeling machineries allow the transition from a repressed state to an active state. Pioneer transcription factors are the first that bind a closed promoter and enhancers that facilitate the access of other sequence-specific transcription factors to these genomic regions. Furthermore, regulatory genomic regions are now understood as dynamic structures showing high turnover of associated transcription factors and their co-regulators. This has a significant impact on the rate of transcription.

In this chapter, we will discuss the impact of chromatin remodeling and nucleosome positioning on the coordinated activation of promoter regions. We will learn that the multi-step process of gene expression is complex and highly dynamic, and in some way can be “noisy”, i.e., there are large cell-to-cell variations. This transcriptional dynamics will be understood as a central step in fine-tuning gene expression.