Chromatin Structure and DNA Packing

Chromatin Structure

• Chromatin is a complex of DNA, proteins (histones and non-histones), and RNA found within the nucleus of eukaryotic cells.
• Chromatin is composed of DNA, approximately 30-40%, protein (50-60%), and RNA (1-10%).
• Metaphase chromosomes contain approximately 15-20% DNA, 10-15% RNA, and 65-75% protein.
• A typical human cell contains 46 chromosomes (23 pairs).
• The human genome is approximately 2 meters in length.

Steps of DNA Packing into Chromosomes

• DNA is tightly wrapped around proteins known as histones to form structures called nucleosomes.
• A nucleosome is the basic structural unit of chromatin. DNA is wrapped twice around a histone core.
• The histone core is composed of 8 histone proteins (octamer).
• The linker DNA connects adjacent nucleosomes, creating a "beads-on-a-string" structure.
• The nucleosomes further coil and condense into chromatin fibers, becoming progressively more compact.
• The chromatin fibers coil further to form chromosomes.

Nucleosomes

• Nucleosomes are structural units consisting of 8 histone molecules (octamer) and 146 base pairs of DNA.
• The histone proteins (H2A, H2B, H3, and H4) are positively charged, interacting with the negatively charged DNA molecule.
• Histone H1 is a linker histone, located outside the nucleosome core. It's attached to the linker DNA, contributing to further DNA packing.

Histone Modifications

• N-terminal ends of histones can be modified (acetylated, methylated, or phosphorylated).
• These reversible modifications influence the binding of histones to DNA.
• These modifications are crucial for gene expression and DNA replication.

Types of Chromatin

• Euchromatin: Light-staining, decondensed, and transcriptionally accessible regions of the genome (roughly 92% of human genome).
• Heterochromatin: Dark-staining, condensed, and gene-poor regions of the genome. It's further categorized as:
  • Constitutive heterochromatin: Always condensed and inactive (found near centromeres and telomeres).
  • Facultative heterochromatin: Can be condensed or decondensed and active at times (e.g., the inactive X chromosome in females).

Chromosome Structure

• Chromosomes are highly condensed structures of DNA. They are observable during cell division.
• Two sister chromatids, joined at the centromere, comprise each chromosome.
• The centromere is a primary constriction. It's darkly stained because it contains a substantial amount of DNA.
• The centromere is positioned differently in various chromosome types:
  • Metacentric: Centromere is in the middle, producing two equal arms.
  • Submetacentric: Centromere is slightly off-center, producing unequal arms.
  • Acrocentric: Centromere is very close to one end, producing a very short and a very long arm.
  • Telocentric: Centromere is on the end, resulting in only one arm.
• Subtelomeric and pericentromeric regions are found adjacent to the telomeres and centromeres respectively.

Chromosome Number

• The normal number of chromosomes for a species is usually consistent but varies between different organisms.
• Human somatic cells (non-reproductive) typically have 46 chromosomes (22 pairs of autosomes and 1 pair of sex chromosomes, either XX in females or XY in males).
• Human germ cells (reproductive cells) have 23 chromosomes (haploid).

Karyotyping

• Karyotyping is a technique used for identifying chromosomes.
• It involves photographing and arranging chromosomes from a dividing cell into pairs based on size, shape, and banding patterns.
• Karyotypes provide information about the number and structure of chromosomes.
• It's used for detecting chromosomal abnormalities (numerical or structural).

Chromosome Banding

• Chromosome banding techniques use special stains (e.g., Giemsa) to produce a characteristic pattern of dark and light bands.
• Bands identify regions within chromosomes.
• Banding helps identify small changes in chromosome structure.

Chromosome Positional Notation

• Positional notation system for a chromosome (e.g. Xq22.3) specifies the chromosome, the arm (p for short, q for long), the band number, and the sub-band number.

Chromosome Size

• Chromosome size varies depending on the stage of cell division.
• Chromosomes are longest and thinnest during interphase and progressively shorter and thicker during prophase and metaphase.
• Chromosome measurements are typically taken during mitotic metaphase.