Dr. Brian David Strahl

Dr. Brian David Strahl a Professor and Vice-chair at the University of North Carolina at Chapel Hill. Dr. Brian Strahl’s lab has been at the forefront of discovering how small chemical additions or molecular “tags” on histone proteins (i.e., covalent modifications) regulate the accessibility of DNA and the genetic information it contains. Histones are central to the organization of our DNA in cells. These proteins come in different types or isoforms such as H3, H4, H2A and H2B, and they work together to package our DNA within the small nuclei of cells. Two copies each of each histone type come together to create what is called an octamer, which wraps about 147 base pairs of DNA around it. This structure (histones + DNA) makes up the basic building block of chromatin, which is called the nucleosome. Strings of nucleosomes come together further to create the chromatin fiber, and these fibers organize further into higher-order chromosome structures that are poorly defined but allow large genomes (e.g., ~3.4 billion base pairs making up the human genome) to fit in the confines of a 2-10 micron nucleus. This extraordinary level of compaction is further aided by the actions of a 5 histone type known as linker histone H1.

With all this compaction, a fundamental question is how our genome is made accessible at the right place and time for all of the fundamental processes that occurs with DNA (such as gene expression, DNA repair and replicating the genome). Importantly, histones, and the nucleosomes they form, govern chromatin compaction and decompaction of our DNA. Just about every process involving the access of our genetic information requires protein machineries to gain access to it. Each of these machineries are highly tuned to interface with, and regulate, the histones that wrap DNA.

Thus, the Strahl lab and others are determining the mechanisms by which histones are regulated to alter the accessibility of DNA, and the types and functions of chemical modifications that are placed on them. Many enzymes have been classified over the last few decades that add (i.e., write) or eliminate (i.e., erase) these histone modifications. The chemical tags serve as signals or messages to inform chromatin how to function (whether to open or close, and/or express a gene or not). The question of how these chemical tags work has been at the core of many researches and studies.