Assembly of DNA into Chromosomes

Overview

Eukaryotic DNA does not exist in cells as a plain double helical molecule. This module examines how DNA is packaged with protein into chromosomes, allowing a large amount of DNA to fit in a cell's nucleus. The ramifications of this on gene activity and chromosome behavior will be examined.

Objectives

1. Understand the nature of chromatin - how DNA and histones interact to form nucleosomes.
2. Know the basic structures of the 10 nm chromatin fiber and the 30 nm chromatin fiber, and understand how each relates to the state of chromosomes during different phases of the cell cycle.
3. Realize that chromosomes are single pieces of DNA packaged into chromatin, and that they are not homogeneous - they consist of interspersed regions of heterochromatin and euchromatin.
4. Know the basic structures of centromeres and telomeres, and the function of each.

Chromatin Structure

DNA does not normally exist as the simple double helix described in the module on DNA structure. Instead, eukaryotic DNA is found packaged with protein, forming a substance called chromatin. There's a good reason for this: the amount of DNA in a single human cell, lined up end to end, would stretch nearly two meters! This DNA has to be compacted enough to fit into a single nucleus, and packaging the DNA into chromatin accomplishes this.

The essential unit of DNA packaging is the nucleosome. A nucleosome consists of a small amount of DNA wrapped up with protein. The proteins that interact with DNA to form chromatin comprise a family of basic (positively charged) proteins called histones. There are five different types of histone protein: H1, H2A, H2B, H3, and H4. Of these, two molecules each of H2A, H2B, H3, and H4 combine to form a histone octamer. DNA wraps around the octamer, making 1 3/4 turns around the protein complex. The amount of DNA associated with the histone octamer is 146 bp. The octamer plus the DNA comprise what is called the nucleosome core. A small stretch of DNA (60 bp) runs between adjacent nucleosome cores, and is known as the linker. A single nucleosome consists of one core plus a linker. The total amount of DNA involved in a single nucleosome is approximately 206 bp. Chromatin therefore consists of DNA wrapped around one histone octamer after another, like a long string of beads (as shown in panel B). In fact, when viewed under an electron microscope, this configuration looks just like beads on a string. This configuration, known as the 10 nm chromatin fiber (based on its approximate diameter), corresponds to the state of chromosomes during interphase, when most of the chromosomes exist as euchromatin.

Chromatin can be packed further into higher-order structures. This involves the action of histone H1. H1 binds to DNA on the outside of nucleosomes (at a ratio of one H1 molecule per nucleosome), then H1 molecules interact with each other, causing the chromatin to form a spiral, with 6 to 8 nucleosomes per turn of the spiral. Imagine taking a string of beads and wrapping it around your finger. This structure is known as a solenoid or 30 nm chromatin fiber (again, based on diameter; shown in panel C). Because the chromatin is so tightly packed, DNA in the 30 nm fiber is genetically inactive (that is, the genes are not functioning). This configuration corresponds to heterochromatin, or the state of chromosomes during cell division. The 30 nm fiber is folded up further (into loops; panels D and E) to make metaphase chromosomes.