DNA in Chromatin

Introduction to DNA Packaging in Chromatin

• Objective: Understanding how DNA is structured and packaged in chromatin.

  • Ability to sketch the structure of DNA at multiple levels.

  • Explanation of how DNA is packaged using histones into chromatin.

  • Description of how this packaging restricts functions on the genome.

Basic Structure of DNA

• Double Helix Model:

  • DNA is commonly represented as a double helix, resembling a twisted ladder.

  • Phosphodiester Bond Formation:

  • Involves a condensation reaction where the 3' hydroxyl group of one nucleotide attacks the 5' phosphate of another nucleotide, forming a phosphodiester bond between the two.

• Antiparallel Structure:

  • The two strands of DNA run in opposite directions (antiparallel), held together by hydrogen bonds between complementary base pairs (C-G and A-T).

• Helical Structure:

  • DNA is not merely a ladder; it is a helical structure which features:

  • Major grooves and minor grooves important for protein binding.

Genome Organization

• Gene Encoding:

  • Not all regions of the genome code for genes; most do not.

  • Only about 2% of the human genome is composed of genes coding for RNA and proteins.

  • The remainder includes regulatory sequences, repetitive sequences, and non-coding DNA.

• Cellular Organization of DNA:

  • DNA is not mainly found in the form of metaphase chromosomes; in most cells, DNA appears as a spaghetti-like structure representing a complex organization.

• Euchromatin vs Heterochromatin:

  • Euchromatin:

  • More open structure, contains fewer proteins, making it more accessible for DNA replication, transcription, and repair.

  • Heterochromatin:

  • More compact and densely packed with proteins, therefore less accessible for cellular machinery involved in replication, transcription, and repair.

Structural Characteristics of DNA

• Physical Dimensions of DNA:

  • The haploid genome is approximately six feet long and must fit within a space of about six micrometers.

  • The DNA molecule is very thin, about 2 nanometers in diameter, allowing it to be compacted without tangling.

DNA Packaging Mechanism

• Nucleosomes:

  • Fundamental units of DNA packaging made up of DNA wrapped around a core of histone proteins (a DNA-protein complex).

  • Histone Types:

  • Four main types: H2A, H2B, H3, and H4, forming an octamer (2 of each type).

  • The DNA wraps around the histone octamer about two times (approximately 150 base pairs).

• Beads on a String Model:

  • Nucleosomes resemble beads on a string when viewed structurally with linker DNA connecting them.

• Dynamic Structures:

  • Nucleosomes interact with one another to create complex and compact structures.

  • Even euchromatin (more accessible) is organized into nucleosomes, thus highlights the importance of organization in genomic accessibility.

Chromatin During Cell Division

• During cell division, DNA undergoes additional compaction to form mitotic chromosomes, recognizable by their typical X-shape structure.

  • Karyotyping:

  • Analysis of mitotic chromosomes involves examining their shape and structure.

Chromosomal Territories and Gene Accessibility

• Chromosome Positioning:

  • Each chromosome occupies a specific territory within the nucleus, influencing accessibility.

  • Euchromatin is generally located more centrally, while heterochromatin is found towards the outside near the nuclear membrane.

Functional Implications of DNA Packaging

• DNA Accessibility for Processes:

  • The organization means that genes needed for transcription or replication are often located within euchromatin, while less active or irrelevant regions are found in heterochromatin.

  • Specific regulatory mechanisms allow cells to overcome the tight packaging and access particular regions for function when necessary.

  • The dynamic nature ensures regions can be opened for transcription or replication and closed when not needed, allowing for regulated control over gene expression and DNA use.