Chromatin is a complex of deoxyribonucleic acid (DNA) and proteins residing within the nucleus of eukaryotic cells. It packages DNA into a compact form within the nucleus. Beyond packaging, chromatin regulates gene expression, influencing nearly every cellular process. Its proper function is important for the development and maintenance of all living organisms.
The Building Blocks of Chromatin
Chromatin’s primary components are DNA and histones. DNA carries the genetic instructions for an organism. Histones are small, positively charged proteins that DNA wraps around. There are five main types of histones, with H2A, H2B, H3, and H4 forming the core, and H1 acting as a linker.
The nucleosome is the fundamental repeating unit of chromatin. Each nucleosome consists of about 147 base pairs of DNA coiled around a core of eight histone proteins (two copies each of H2A, H2B, H3, and H4). These nucleosomes are connected by “linker” DNA, creating a “beads-on-a-string” structure. This initial compaction reduces DNA length by about seven-fold, making it the first step in fitting genetic material into the nucleus.
How Chromatin Organizes DNA
The “beads-on-a-string” nucleosome structure is the initial stage of DNA compaction within the nucleus. These nucleosomes organize into more compact arrangements. One level of organization is the 30-nanometer fiber, where nucleosomes coil or stack. This compaction, through models like solenoid or zigzag, further reduces DNA length.
Beyond the 30-nanometer fiber, chromatin organizes at higher levels. These include large loops, anchored to a nuclear protein scaffold, and topologically associating domains (TADs). These structures progressively compact DNA, allowing the two-meter human genome to fit within a 5-10 micrometer nucleus. This organization ensures genetic material remains stable and accessible for reading or replication.
Chromatin’s Role in Gene Control
Chromatin actively dictates which genes are accessible for expression. Compact chromatin restricts cellular machinery from reaching DNA sequences, effectively turning genes “off.” When a gene needs expression, its chromatin must open, allowing transcription factors and RNA polymerase to bind to the DNA. This dynamic process is tightly regulated.
Chemical modifications to histones alter chromatin structure and influence gene activity. For instance, acetylation often loosens histone-DNA interaction, leading to an open, transcriptionally active state (euchromatin). Conversely, methylation can lead to a condensed, transcriptionally repressed state (heterochromatin), depending on the specific histone modified. These modifications signal the cell’s machinery to activate or silence genes.
Chromatin and Health
Chromatin function is important for cellular processes like cell division, differentiation, and organismal development. Chromatin-mediated gene expression ensures cells perform correct functions. Disruptions in chromatin organization or regulation can have significant health consequences.
Errors in chromatin structure or histone-modifying enzymes can lead to health issues. For example, dysregulation of chromatin-modifying enzymes links to developmental disorders, disrupting gene activation during embryonic growth. Alterations in chromatin organization are also seen in cancers, leading to inappropriate activation of growth-promoting genes or silencing of tumor-suppressor genes.