Epigenetic Regulation of Chromatin Structure and Dynamics
DNA encodes the information for the RNA and protein molecules of all living things. Furthermore, all the cells of an individual organism contain the same DNA sequence, yet the cells of higher organisms form a diverse array of types, including those for the skin, brain, and bones. Clearly, these varying phenotypes arise from differences beyond the genetic sequence, and are therefore referred to as "epigenetics." As a long, highly-charged, and semi-flexible polymer, the DNA of higher life is packaged with histone proteins into an array of nucleosomes and form what is known as chromatin. Recent experiments revealed that small chemical changes to DNA and the disordered tails of histone proteins, known as epigenetic modications, play an important regulatory role in gene expression in vivo, and modulate chromatin structure and dynamics in vitro. However, the underlying mechanism governing this regulation remains relatively unknown. Here, we propose a set of landmark simulations that will determine how epigenetic modications influence histone tails' interactions with nucleosomal DNA, with the structured part of the histone proteins, and with other histone tails. The outcome of these simulations will quantitatively characterize each of the above interactions and predict their relative contributions to forces that determine large-scale organization of chromatin fibers. Lastly, resulting MD trajectories will be used to complete a mesoscale model of chromatin which will permit us to determine, for the first time, the response of an entire chromatin fiber to tension or torsional stress that are thought to regulate large-scale dynamics of chromatin in the nucleus.