Specificity of the HP1 chromo domain for the methylated N-terminus of histone H3

Steven A. Jacobs, Sean Dixon Taverna, Yinong Zhang, Scott D. Briggs, Jinmei Li, Joel C. Eissenberg, C. David Allis, Sepideh Khorasanizadeh

Research output: Contribution to journalArticle

Abstract

Recent studies show that heterochromatin-associated protein-1 (HP1) recognizes a 'histone code' involving methylated Lys9 (methyl-K9) in histone H3. Using in situ immunofluorescence, we demonstrate that methyl-K9 H3 and HP1 co-localize to the heterochromatic regions of Drosophila polytene chromosomes. NMR spectra show that methyl-K9 binding of HP1 occurs via its chromo (chromosome organization modifier) domain. This interaction requires methyl-K9 to reside within the proper context of H3 sequence. NMR studies indicate that the methylated H3 tail binds in a groove of HP1 consisting of conserved residues. Using fluorescence anisotropy and isothermal titration calorimetry, we determined that this interaction occurs with a KD of ∼100 μM, with the binding enthalpically driven. A V26M mutation in HP1, which disrupts its gene silencing function, severely destabilizes the H3-binding interface, and abolishes methyl-K9 H3 tail binding. Finally, we note that sequence diversity in chromo domains may lead to diverse functions in eukaryotic gene regulation. For example, the chromo domain of the yeast histone acetyltransferase Esa1 does not interact with methyl-K9 H3, but instead shows preference for unmodified H3 tail.

Original languageEnglish (US)
Pages (from-to)5232-5241
Number of pages10
JournalThe EMBO journal
Volume20
Issue number18
DOIs
StatePublished - Sep 17 2001
Externally publishedYes

Fingerprint

Histones
Tail
Chromosomes
Proteins
Histone Code
Nuclear magnetic resonance
Polytene Chromosomes
Histone Acetyltransferases
Calorimetry
Fluorescence Polarization
Gene Silencing
Titration
Gene expression
Yeast
Drosophila
Fluorescent Antibody Technique
Anisotropy
Genes
Yeasts
Fluorescence

Keywords

  • Chromo domain
  • Esa1
  • Heterochromatin-associated protein 1 (HP1)
  • Histone tail
  • Lysine methylation

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

Cite this

Jacobs, S. A., Taverna, S. D., Zhang, Y., Briggs, S. D., Li, J., Eissenberg, J. C., ... Khorasanizadeh, S. (2001). Specificity of the HP1 chromo domain for the methylated N-terminus of histone H3. The EMBO journal, 20(18), 5232-5241. https://doi.org/10.1093/emboj/20.18.5232

Specificity of the HP1 chromo domain for the methylated N-terminus of histone H3. / Jacobs, Steven A.; Taverna, Sean Dixon; Zhang, Yinong; Briggs, Scott D.; Li, Jinmei; Eissenberg, Joel C.; Allis, C. David; Khorasanizadeh, Sepideh.

In: The EMBO journal, Vol. 20, No. 18, 17.09.2001, p. 5232-5241.

Research output: Contribution to journalArticle

Jacobs, SA, Taverna, SD, Zhang, Y, Briggs, SD, Li, J, Eissenberg, JC, Allis, CD & Khorasanizadeh, S 2001, 'Specificity of the HP1 chromo domain for the methylated N-terminus of histone H3', The EMBO journal, vol. 20, no. 18, pp. 5232-5241. https://doi.org/10.1093/emboj/20.18.5232
Jacobs, Steven A. ; Taverna, Sean Dixon ; Zhang, Yinong ; Briggs, Scott D. ; Li, Jinmei ; Eissenberg, Joel C. ; Allis, C. David ; Khorasanizadeh, Sepideh. / Specificity of the HP1 chromo domain for the methylated N-terminus of histone H3. In: The EMBO journal. 2001 ; Vol. 20, No. 18. pp. 5232-5241.
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