Chromatin: Structure, Composition, and Function

• Chromatin is the combination of DNA and proteins that make up the contents of the nucleus of a cell
• Its primary function is to compress the DNA into a compact form to fit inside the nucleus
• Additionally, it protects the DNA from damage and regulates gene expression and DNA replication
• Chromatin structure varies depending on the cell's stage of the cell cycle

Chromatin Composition

• Consists of DNA, proteins (histones and non-histone proteins), and RNA
• DNA carries the genetic information
• Histones are proteins responsible for the first level of DNA packaging
• Non-histone proteins are involved in gene regulation, DNA replication, and DNA repair
• RNA is involved in gene expression

Histones

• Are small, positively charged proteins that bind to the negatively charged DNA
• The positive charge is due to a high proportion of lysine and arginine amino acids
• There are five main types: H1, H2A, H2B, H3, and H4
• H2A, H2B, H3, and H4 form the nucleosome core
• H1 binds to the nucleosome and linker DNA, stabilizing the chromatin structure
• Histones are subject to various modifications, such as acetylation, methylation, phosphorylation, and ubiquitination

Nucleosomes

• Are the basic units of chromatin
• Consist of approximately 146 base pairs of DNA wrapped around a core of eight histone proteins (two each of H2A, H2B, H3, and H4)
• The DNA between nucleosomes is called linker DNA, which is bound by histone H1
• Nucleosomes resemble "beads on a string"

Levels of Chromatin Organization

• DNA wraps around histone proteins forming nucleosomes (10 nm fiber)
• Nucleosomes coil up to form a 30 nm fiber
• The 30 nm fiber forms looped domains, which attach to proteins
• These looped domains further coil and fold, resulting in the highly condensed chromosomes seen during cell division

Euchromatin

• Is a lightly packed form of chromatin that is rich in gene concentration, and is often (but not always) under active transcription
• Represents the most active portion of the genome
• Is typically found in the actively transcribed regions of the genome

Heterochromatin

• Is a tightly packed form of chromatin, which comes in multiple varieties
• Constitutive heterochromatin is permanently condensed and contains repetitive sequences
• Facultative heterochromatin can become euchromatin

Chromatin Remodeling

• Is the dynamic modification of chromatin architecture to allow access of condensed genomic DNA to regulatory proteins complexes
• ATP-dependent chromatin remodeling complexes use the energy of ATP hydrolysis to alter histone-DNA contacts
• Histone modifying enzymes add or remove chemical groups to or from histones (acetylation, methylation, phosphorylation, and ubiquitination)

Histone Modifications

• Covalent modifications to histone proteins that influence chromatin structure and gene expression
• Acetylation is associated with increased gene expression
• Methylation can either increase or decrease gene expression, depending on the specific amino acid modified
• Phosphorylation is typically associated with gene expression and chromosome condensation
• Ubiquitination is involved in gene expression, DNA repair, and chromosome condensation

Chromatin and Disease

• Aberrant chromatin structure and modifications are associated with various diseases, including cancer and genetic disorders
• Mutations in histone modifying enzymes can lead to altered gene expression patterns and disease development
• Epigenetic drugs that target histone modifying enzymes are being developed as potential cancer therapies

Summary

• Chromatin is a dynamic structure whose organization plays a crucial role in regulating gene expression and maintaining genome stability
• Chromatin structure is influenced by histone modifications and chromatin remodeling complexes
• Aberrant chromatin structure and modifications are associated with various diseases