Chromatin proteins: key responders to stress

Abstract

Environments can be ever-changing and stresses are commonplace. In order for organisms to survive, they need to be able to respond to change and adapt to new conditions. Fortunately, many organisms have systems in place that enable dynamic adaptation to immediate stresses and changes within the environment. Much of this cellular response is coordinated by modulating the structure and accessibility of the genome. In eukaryotic cells, the genome is packaged and rolled up by histone proteins to create a series of DNA/histone core structures known as nucleosomes; these are further condensed into chromatin. The degree and nature of the condensation can in turn determine which genes are transcribed. Histones can be modified chemically by a large number of proteins that are thereby responsible for dynamic changes in gene expression. In this Primer we discuss findings from a study published in this issue of PLoS Biology by Weiner et al. that highlight how chromatin structure and chromatin binding proteins alter transcription in response to environmental changes and stresses. Their study reveals the importance of chromatin in mediating the speed and amplitude of stress responses in cells and suggests that chromatin is a critically important component of the cellular response to stress.

Figure 1. Cellular responses to stress and environmental factors.

Stresses such as heat shock are sensed by factors located inside of or outside of the cell (1). In the case of HSF1, it relays the message to the nucleus (2) to strongly increase the transcription of genes involved in fixing protein shape (3). RNA stability (4) and protein production levels (5) are also important factors determining the response to stress. Protein activity (6), such as the chaperones induced by heat shock, is critical in mediating the response. In higher eukaryotes, cells may send signals (7) to neighboring cells to assist in mounting a larger stress response encompassing many cells and tissues.

Figure 2. Chromatin structure and binding proteins can affect transcription through multiple avenues.

Chemical additions can be made to histones by chromatin-modifying enzymes such as Set1, which adds methyl groups to a specific place on the histone (1); many of these chemical modifications can be removed by other proteins (2). Some proteins bind to specific modifications on histones that have been added (3). Nucleosome spacing (4) can be altered by chromatin remodelers that use the power of ATP to drive movement and histone chaperones (5) can remove and replace histones on DNA. All of these factors can control access of the DNA and chromatin to other factors, such as transcription factors that may need to bind open pieces of DNA (6). This is a dynamic process requiring many proteins to act in concert as appropriate.