A single human cell contains over six feet of DNA, which must be meticulously packaged to fit inside the cell’s nucleus. This feat of data compression is accomplished by wrapping the DNA around protein spools, creating a structure called chromatin. The fundamental unit of this packaging is the nucleosome, which organizes the genome and plays a role in how genetic information is used. This organization prevents the DNA from becoming a tangled mess, ensuring that specific segments can be accessed when needed.
The Nucleosome Core Particle
The foundational component of chromatin is the nucleosome core particle, a highly conserved structure across species. This particle is a spool around which the DNA thread is wound. The spool itself is an octamer composed of eight histone proteins: two copies each of H2A, H2B, H3, and H4. These proteins assemble into a stable, disc-like structure.
A precise length of DNA, approximately 147 base pairs (bp), makes about 1.67 left-handed turns around this histone octamer. This wrapping is not random, as the histone octamer’s structure forces the DNA to bend sharply, achieving the first level of genomic compaction.
The resulting structure is a cylinder measuring about 11 nanometers in diameter and 5.5 nanometers in height. The histone proteins have flexible “tails” that extend from this core structure. These tails are important for interactions between neighboring nucleosomes and for receiving chemical modifications that can alter chromatin structure and function.
Linker DNA and Repeat Length
The nucleosome cores are connected by stretches of DNA known as linker DNA, creating a “beads-on-a-string” structure that forms the primary 10-nanometer fiber of chromatin. The presence of this linker DNA introduces variability into nucleosome spacing.
The length of the linker DNA is not fixed, ranging from 10 to over 80 base pairs and varying between species, tissues, and even along a single chromosome. The combined length of the core particle DNA and the linker DNA is known as the nucleosome repeat length (NRL). The NRL is calculated by adding the consistent ~147 bp of the core to the variable length of the linker DNA.
The term nucleosome “size” or “spacing” refers to this nucleosome repeat length (NRL). An NRL can range from around 157 bp to over 240 bp. This variation has significant implications for how DNA is folded into more complex structures.
Regulation of Nucleosome Spacing
The spacing between nucleosomes, defined by the length of the linker DNA, is actively managed by specific proteins. One main regulator is the linker histone, H1. Unlike the core histones, H1 is not part of the octamer but binds to the DNA where it enters and exits the nucleosome core. This binding stabilizes the wrapped DNA, draws adjacent nucleosomes closer, and different H1 subtypes can compact chromatin to varying degrees.
Chromatin remodeling complexes also control nucleosome spacing. These large, multi-protein machines use energy to slide nucleosomes along the DNA. This action pushes them closer together or pulls them farther apart, changing the length of the exposed linker DNA and dynamically altering the local chromatin landscape.
The actions of linker histones and chromatin remodelers work together to establish and maintain specific nucleosome spacing. These mechanisms ensure the chromatin structure is not static but can be adjusted in response to the cell’s changing needs, such as requiring access to a specific gene.
How Spacing Influences DNA Function
The distance between nucleosomes directly impacts the accessibility of the underlying DNA. When nucleosomes are packed tightly with short linker DNA, the genetic material condenses into a state known as heterochromatin. In heterochromatin, the DNA is less accessible to the cellular machinery responsible for reading genes, leading to gene silencing. These regions are often transcriptionally repressed.
Conversely, when nucleosomes are spaced farther apart with longer linker DNA, the chromatin is in an open state called euchromatin. This relaxed configuration exposes the DNA, allowing transcription factors, DNA repair enzymes, and other proteins to bind to their target sequences. Consequently, regions with wider nucleosome spacing are associated with active genes being transcribed into RNA.
The physical spacing of nucleosomes acts as a gatekeeper for genetic information. Loosely packed euchromatin is considered “open for business,” allowing for active gene expression, while tightly packed heterochromatin is “closed,” keeping genes in a silent state. Studies show that hepatocyte DNA, with longer linkers, is more accessible than yeast DNA, which has shorter linkers, underscoring that nucleosome spacing is a determinant of DNA accessibility.