U01.01.001 Chromatin structure

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Learning Objectives

  • Describe the nucleosome unit and the role of H1 linker histones.
  • Contrast the physical and transcriptional properties of Heterochromatin and Euchromatin.
  • Explain the biochemical effects of DNA methylation and Histone acetylation on gene expression.
  • Identify the unique properties of Mitochondrial DNA.

DNA Packaging: “Beads on a String.”

To fit into the nucleus, DNA is organized into increasingly condensed levels of chromatin.

  • The Nucleosome: The fundamental unit. DNA loops twice around a histone octamer (2x H2A, H2B, H3, H4).
  • H1 Histone: The “Linker” histone. It binds to the nucleosome and linker DNA to stabilize the fiber.
  • Charge Interaction: DNA is negatively charged (phosphate groups). Histones are positively charged (rich in Lysine and Arginine).

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Heterochromatin vs. Euchromatin

Feature Heterochromatin (H) Euchromatin (E)
Condensation Highly condensed (“Hidden”) Less condensed
EM Appearance Darker; often at nuclear periphery Lighter
Transcription Inactive (Sterically inaccessible) Active (Expressed)
Example Barr Bodies (Inactive X) Actively transcribed genes

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DNA and Histone Modifications

Epigenetic changes regulate gene expression without altering the DNA sequence.

DNA Methylation

  • Action: Methyl groups are added to CpG islands within promoter regions.
  • Result: Mutes (Silences) transcription.
  • Mnemonic: CpG methylation makes DNA Mute.
  • Clinical: Implicated in Fragile X syndrome and genomic imprinting.

Histone Acetylation

  • Action: Acetyl groups remove the histone’s positive charge, relaxing the coiling.
  • Result: Active (Stimulates) transcription.
  • Mnemonic: Acetylation makes DNA Active.

Histone Deacetylation

  • Action: Removal of acetyl groups, restoring positive charge and tightening DNA coiling.
  • Result: Deactivates transcription.
  • Clinical: Dysregulated in Huntington’s disease.

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Mitochondrial DNA (mtDNA)

  • Shape: Circular (unlike linear nuclear DNA).
  • Histones: Do not bind histones.
  • Origin: Inherited maternally.

 

 

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