Histone acetylation Chromatin modification What does histone acetylation do

Histone Acetylation

  • Histone acetylation is a modification of chromatin that can alter gene expression patterns.

  • Chromatin is composed of nucleosomes, each containing histones and DNA. The accessibility of DNA is influenced by how tightly it is wrapped around histones.

Characteristics of Histones

  • Histones are basic proteins with a conserved histone fold region and a tail that serves as a modification site.

  • Modifications include acetylation, methylation, phosphorylation, ubiquitinylation, etc.

  • Acetylation primarily occurs on lysine residues in histones.

Enzymatic Action

  • Histone acetylation is catalyzed by histone Acetyltransferase, which transfers an acetyl group from Acetyl CoA to histone tails.

  • This modification masks the positive charge of histones, weakening their electrostatic interaction with negatively charged DNA phosphate groups.

Consequences of Acetylation

  • Loosened DNA-histone interactions increase accessibility to key proteins:

    • Transcription factors and chromatin remodelers can bind, facilitating changes in transcription and chromatin landscape.

  • Specific sites of acetylation (e.g., H4 lysine 8 or 16) are associated with active gene expression, while others (e.g., H4 lysine 5-12) correlate with newly synthesized histones ready to form new nucleosomes.

Histone Code

  • Acetylated histones often correlate with euchromatin, which is active in gene expression, while heterochromatin typically lacks acetylated histones.

  • Histone modifications establish a histone code, which is interpreted by specific proteins:

    • Writers: Histone acetyltransferases (add acetyl groups).

    • Readers: Bromodomain-containing proteins that bind to acetylated histones.

    • Erasers: Histone deacetylases (remove acetyl groups).

Proteins Involved

  • Proteins with bromodomains include transcription factors and nucleosome remodelers, facilitating chromatin changes.

  • Notable acetyltransferase complexes include the SAGA complex (with GCN5 as the active domain) and p300/CBP complexes, each targeting specific histones.

Summary

  • Histone acetylation modifies chromatin structure and function by impacting DNA-histone interactions, mediated by histone acetyltransferases (writers), deacetylases (erasers), and bromodomain proteins (readers).

  • The location and type of acetylation affect the chromatin landscape and gene expression accordingly.