Role of Chromatin Remodeling and DNA Modification in Transcriptional Regulation

Abstract

Synopsis Control of gene expression begins with rendering DNA more or less accessible to the transcription machinery. DNA is packaged around histones and other proteins to form chromatin. Histones condense DNA but also limit its accessibility to the transcription machinery. DNA that is packaged tightly and inaccessible to transcription machinery is referred to as heterochromatin, while loosely packaged DNA that can be transcribed is termed euchromatin. Since transcription depends upon accessible DNA, chromatin modification provides a powerful means for the cell to regulate gene expression. Indeed, chromatin state is dynamic, changing over time or due to alterations in the cell's environment. Chromatin state varies between cell types and is one way that cells in different tissues show unique patterns of gene expression. Importantly, chromatin state is altered in many diseases, including cancer. Proper regulation of chromatin state is important for maintaining healthy gene expression. Chromatin accessibility can be altered by modifying either the DNA itself or the proteins that package it. Such modifications are highly dynamic and reversible. Some modifications correlate with loose chromatin and active transcription, while other modifications correlate with tight chromatin and inhibited transcription. However, these correlations are not absolute and the causal relationships between the modifications and transcription efficiency are not clear. These modifications are numerous and potentially interconnected, forming an intricate network of transcriptional control. Some modifications persist into the next generation, affecting the transcription of the organism's offspring.