Histones and Histone Deacetylases

Epigenetics is an increasingly big deal in biological discovery. We are regularly reading about the influence of actions peripheral to DNA in regulating DNA transcription and translation. We are learning that mice may fear what grandparent mice feared (Kelly’s blog ), due to heritable changes in DNA. In term of one of several mechanisms of epigenetic change, we are learning much about histone deacetylases and their role in gene regulation, as well as disease (Isobel’s blog ). In this blog, let’s take a step back and look at histones, and how they are influenced by acetylation/deacetylation.

The Role of Histones
Histones are proteins found in the nucleus of eukaryotic cells, where they package DNA into nucleosomes. Histones make up the main protein component of chromatin, acting as spool-like structures around which DNA wraps.

There are five major histone classes,three of these are core histones, the other two are called linker histones. Core histones comprise the core of the nucleosome, around which DNA is wrapped, while the linker histones bind at the entrance and exit sites of the DNA, so as to lock it into place. The linker histones also enable a higher order of structure. If you hold both ends of a rubber band, and twist one end, you’ll see that the rubber band twists and folds over itself; the end being held steady enables this twisting and folding: this is how the linker histones work. Histone-DNA structure is frequently represented as a beaded chain-type image (see figure).

DNA wrapping around histones in a bead and chain-like fashion.
DNA wrapping around histones in a bead and chain-like fashion.

Histone and DNA: Charged Interactions
Histone tails normally carry a positive charge due to amine groups present on their lysines and arginines. This positive charge is the means by which histone tails interact with and bind to the negatively-charged phosphate groups on the DNA backbone.

Histones are subject to post-translational modifications, primarily on their N-terminal tails, by enzymes. Such modifications include methylation, citrullination, acetylation, phosphorylation, SUMOylation, ubiquitination, and ADP-ribosylation. Such modifications can affect histone function in gene regulation. Acetylation is one of the most common post-translational modifications of histones (1). Continue reading “Histones and Histone Deacetylases”

Epigenetics and Exercise

Turning on some genes
Turning on some genes

If, like me, you sometimes need more motivation to exercise consistently—even though you know that it is good for you—you may be interested in the findings of a paper published recently in PLOS Genetics. The paper showed that consistent exercise over a 6-month period caused potentially beneficial changes in gene expression. In short, regular exercise caused expression of some “good” genes, and repression of “bad” ones, and these changes appeared to be controlled by epigenetic mechanisms.

Epigenetic changes are modifications to DNA that affect gene expression but don’t alter the underlying sequence. Perhaps the best understood example of an epigenetic change is DNA methylation—where methyl groups bind to the DNA at specific sites and alter expression, often by preventing transcription. Epigenetic changes have been shown to occur throughout all stages of development and in response to environmental factors such as diet, toxin exposure, or stress. The study of epigenetics is revealing more and more about how the information stored in our DNA is expressed in different tissues at different times and under different environmental circumstances. Continue reading “Epigenetics and Exercise”