Chromatin Composition and Structure

Chromatin is a molecular complex composed of DNA and proteins, primarily histones, which are permanent components throughout the cell’s life. Other molecules transiently associate with chromatin during cell formation, including various types of RNA (rRNA, tRNA, and mRNA), enzymes involved in transcription and replication (polymerases), enzymes involved in condensation cycles, and enzymes that regulate gene expression. Therefore, chromatin is a dynamic structure.

The composition of chromatin is: RNA + DNA + Protein

DNA

DNA is the most important component of chromatin from a structural and functional standpoint. It is the repository of genetic information, transcribed from mother to daughter cells without losing information.

  • Primary structure: The linear chain of nucleotides joined by phosphodiester bonds in the 5′ – 3′ direction. Two chains form an antiparallel structure.
  • Secondary structure: The spatial arrangement showing double-stranded DNA in a double helix shape.
  • Tertiary structure: DNA is wound around histones to form chromatin (euchromatin).
  • Quaternary structure: Chromatin is further folded to form chromosomes (heterochromatin).

Methods of Studying DNA

Molecular probes for detection: When DNA is heated above 100°C or subjected to high pH, the double helix unfolds, and the two chains separate. There are two types of probes:

  • Heterogeneous probes: Denatured DNA is fragmented into small, single-stranded segments of uniform size but different sequences, and then renatured. This method measures the speed and rate of reassociation of single-strand chains.
  • Homogeneous probes: These are more specific. A known DNA sequence is used to collide with an unknown single-stranded DNA chain.

Restriction enzymes or nucleases: These act like scissors, cutting specific sequences of 4 to 6 nucleotides. They are used to cut DNA, subjecting it to electrophoresis for sequence analysis.

Electron microscopy of DNA: These methods reveal three types of sequences in DNA:

DNA Sequence Types

  • Highly dispersed repetitive sequences: Account for 5% of the human genome. The repeating unit is 300 base pairs (bp) long, with 500,000 copies in humans.
  • Highly repetitive sequences: Account for 6% of the human genome. Short sequences are grouped into blocks and are identical. The repeating unit is between 1-10 bp. These are designated as satellite DNA:
    • Regular satellite DNA (105-107)
    • Minisatellite DNA (100-105)
    • Microsatellite DNA (10-100)
    Their mission is structural, located in centromeric and telomeric DNA.
  • Moderately repetitive sequences: Account for 25-40% of the human genome. These are sequences of 100-105 bp, with similar or identical copies distributed throughout the genome. Types include:
    • Multigene Families: Similar or identical genes that evolve from a common ancestral gene (e.g., rRNA, tRNA, histones, hemoglobin, immunoglobulin). These are repeated millions of times.
    • Pseudogenes: Structurally similar to functional genes but lack regulatory sequences and cannot be expressed. They arise from a common ancestral gene that has been duplicated multiple times.
    • Amplified genes: Originate from a common ancestral gene with multiple duplications. For example, rDNA is duplicated in the genome and nucleoplasm to allow more rRNA transcription during embryonic development.
    • Transposons (mostly): A transposon is a DNA sequence that can move to different parts of the genome. Retrotransposons transcribe DNA into RNA, then use reverse transcriptase to convert it back into DNA.
  • Unique sequences: Account for 50% of the human genome. These represent genes for all structural proteins and enzymes.

RNA

RNA molecules are transient components of chromatin during its genesis. They carry genetic information from the nucleus to the cytoplasm. All RNA is derived by transcription of chromosomal DNA. The primary sequences transcribed from DNA to the cytoplasm are rRNA, mRNA, and tRNA. Nuclear RNA degrades rapidly (more labile).

Proteins

Proteins can associate transiently with DNA (enzymes) or permanently (histones). They are fundamental to the origin of chromatin, its evolution to the chromosome, and the operation and control of genetic activity.