Chromatin is a complex of DNA and protein responsible for packaging the incredibly long DNA molecule into the microscopic confines of the cell nucleus. This structural organization not only stores genetic material but also organizes the genome to regulate when and how specific genes are used. Understanding the hierarchical structure of chromatin begins with identifying the first step in this process of genetic condensation.
The Necessity of DNA Condensation
The need for DNA packaging is clear when considering the scale of the human genome. If the DNA from a single human cell were stretched out, it would measure approximately two meters long. This immense length must fit inside a nucleus only a few micrometers in diameter.
DNA condensation achieves an initial compaction ratio of about six-fold. This organization prevents the DNA strands from tangling, which would make it impossible for the cell to access or duplicate its genetic instructions. Packing also protects the DNA structure from damage, especially during cell division.
The Nucleosome: Structure of the First Order
The first order of chromatin packing is the formation of the nucleosome, which serves as the repeating subunit of the chromatin structure. When viewed under an electron microscope, a chain of nucleosomes resembles “beads-on-a-string,” with the DNA acting as the connecting string between the protein beads. This basic structure is conserved across nearly all eukaryotic life forms.
The “bead” is formed by a core of protein around which the DNA double helix is tightly wound. This central protein core is the histone octamer, composed of two copies each of four core histone proteins: H2A, H2B, H3, and H4. These histones are small, positively charged proteins that strongly associate with the negatively charged phosphate backbone of the DNA.
Approximately 147 base pairs of DNA are wrapped around the histone octamer, making about 1.65 turns in a left-handed superhelix. This compact structure forms the nucleosome core particle, which is roughly 11 nanometers in diameter. Adjacent core particles are connected by a short stretch of DNA called linker DNA, typically ranging from 10 to 80 base pairs.
Regulation and Accessibility in Initial Packing
Nucleosome formation introduces a mechanism for regulating gene expression. When DNA is tightly wrapped around the histone core, it physically restricts access to the genetic code. This densely packed state is referred to as heterochromatin.
Conversely, genes that need to be read must be in a looser, more accessible state known as euchromatin. The cell controls this accessibility through dynamic chemical modifications to the histone proteins. These proteins have flexible extensions, called histone tails, that protrude from the nucleosome core and are exposed for modification.
Chemical groups, such as acetyl or methyl groups, can be added to these tails, signaling the cell to either loosen or tighten the DNA wrapping. For instance, adding an acetyl group to a lysine residue removes its positive charge, reducing the attraction between the histone and the negatively charged DNA. This loosening allows transcription factors and other necessary proteins to bind to the DNA, enabling gene activation.