chromatin structure

Eukaryotic Chromatin Structure Overview

Introduction

  • Focus: Eukaryotic chromatin structure at the nucleosome level.

  • Presenter: Dr. F Liu.

Evolution of Eukaryotic Cells

  • Transition from prokaryotic to eukaryotic single-celled organisms took about 2 billion years.

  • Significant milestones in Earth’s geological history:

    • Formation of Earth and Moon,

    • Development of oceans,

    • Emergence of oxygen-producing bacteria,

    • Appearance of sulfate-reducing bacteria and first eukaryotes.

Cell Structures

  • Nucleus: Defines eukaryotic cells as membrane-bound organelles containing genomic DNA.

  • Key differences:

    • Prokaryotic cells: 0.1 - 10 μm in size, have nucleoid regions without membrane;

    • Eukaryotic cells: 10 - 100 μm in size, contain a nucleus, and ribosomes.

Genome Size

  • Eukaryotic genomes are substantially larger than prokaryotic ones (2-1000x size differential).

  • Comparison of genomic sizes among organisms:

    • Mammals: ~6,000,000,000 bp,

    • Arabidopsis: ~135,000,000 bp,

    • Yeast: ~10,600,000 bp,

    • E. coli: ~4,700,000 bp.

Challenges of Large Genomes

  • Compartmentalizing large DNA into a nucleus (extremely compact structure).

  • Ensuring accurate DNA duplications and separations during cell division.

  • Coordinating gene expression effectively.

Prokaryotic DNA Compression

  • Prokaryotes use supercoiling to condense DNA:

    • Mechanism involves HU proteins aiding in DNA compaction.

Historical Discoveries

  • Chromosomes:

    • Walther Flemming (1882): Discovered chromosome structures during mitosis but did not connect chromatin to genetics.

    • Walter S. Sutton: Proposed chromosomes as hereditary units in 1903.

Mitosis and Meiosis

  • Mitosis: Chromosomes are duplicated and equally distributed to daughter cells.

  • Meiosis: One duplication followed by two divisions leading to halved chromosome numbers, restored during fertilization.

Chromatin vs. Chromosome

  • Distinction between chromatin (the relaxed form of DNA) and chromosomes (the condensed form).

Chromatin Structure

  • Primary Structure: Chromatin's structure often described as "beads on a string" originating from the organization of nucleosomes.

  • Ada and Donald Olins (1974): Described primary structure using chicken chromatin.

Histone Proteins

  • Histones account for about 50% of nuclear protein content, amassing positively charged residues (lysine and arginine).

  • Histones are highly conserved across eukaryotes.

Nucleosome Formation

  • Nucleosomes: Basic unit of eukaryotic chromatin formed by an octamer core of histone proteins;

    • Consists of H2A, H2B, H3, and H4 allowing around 146 bp of DNA to wrap around.

Nucleosome Dynamics

  • Flexibility: Histone tail extensions are flexible, contributing to interactions with DNA.

  • Occupancy and Positioning: Nucleosome formation occurs preferentially on genomic segments;

    • The "nucleosome code" theorizes associations between nucleosome positioning and DNA sequences.

  • Mapping Occupancy: Nucleosome occupancy correlates with gene expression and can be mapped using DNase sequencing techniques.

Chromatin States

  • Euchromatin vs. Heterochromatin:

    • Euchromatin: Active regions; less compact and accessible for transcription.

    • Heterochromatin: Tightly packed; generally transcriptionally silent.

Chromatin Remodeling

  • Nucleosome remodelling complexes adjust histone cores to facilitate dynamic chromatin structure.

  • ATP-dependent processes enable repositioning of nucleosomes during processes like transcription and replication.

Hierarchical Chromosome Structure

  • Chromosomes form from chromatin during cell division:

    • Nucleosome assembly leads to DNA loops and further condensation into chromatids.

Key Points

  • Structure of nucleosomes involves a histone core and wrapped DNA sequences.

  • Dynamic regulation of nucleosome positioning impacts gene access and expression.

  • Interphase chromatin consists of euchromatin and heterochromatin domains for varied functionality.

Conclusion

  • Explore implications of genomic DNA packing in eukaryotes, as well as associated benefits and challenges.

  • Further reading: Watson's Molecular Biology of the Gene, 7th Edition, Chapter 8.