Sunday, February 9, 2014

Packing it in: DNA and its place in the nucleus


Attribution: Darryl Leja, NHGRI.





















More than just the hereditary material, DNA is in constant use within cells.  DNA is a dynamic substance; the quintessential double-helix is in constant and intimate connection with other molecules, namely protein complexes known as nucleosomes that are composed of histones.  DNA coils around histones, which in turn coil and form higher-order structures as well.  This all creates a complicated three-dimensional environment in which DNA is not easily accessible at all times. 
















The Nucleosome.  Attribution: Richard Wheeler
[CC-BY-SA-3.0 or GFDL], via Wikimedia Commons.

This combination of DNA and associated proteins is known as chromatin and it is chromatin that allows for fine-tuned regulation of gene expression.  Both DNA and histones in chromatin are the targets of modifications.  The addition of chemical groups, such as methyl moieties, changes the properties and accessibility of DNA within chromatin.  As not every gene is expressed at all times and in all tissues, the complex combination of chemical modifications in chromatin sets up the mechanism by which gene expression is regulated, this often called the chromatin code.   By adding methyl or acetyl groups to the ends of histone molecules, the so-called histone tails, the degree to which those tails can physically interact with nearby DNA is altered.  This creates two fundamental types of chromatin: euchromatin and heterochromatin.  In a euchromatic state, histone molecules are associated with DNA but not so tightly as to preclude the molecular machinery responsible for gene expression from accessing the DNA, thereby allowing for gene expression and RNA production.  In contrast, heterochromatin is very tightly packaged and dense, and therefore genes associated with heterochromatin are thought to be blocked from expression.  

There are many great resources available regarding DNA and chromatin and its function in biology, including the ModEncode EducationalSupplement.