Dynamic regulation of effector protein binding to histone modifications: The biology of HP1 switching

Holger L. Dormann, Shan Tseng Boo, C. David Allis, Hironori Funabiki, Wolfgang Fischle*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

48 Scopus citations

Abstract

Post-translational modifications of histone proteins, the basic building blocks around which eukaryotic DNA is organized, are crucially involved in the regulation of genome activity as they control chromatin structure and dynamics. The recruitment of specific binding proteins that recognize and interact with particular histone modifications is thought to constitute a fundamental mechanism by which histone marks mediate biological function. For instance, tri-methylation of histone H3 lysine 9 (H3K9me3) is important for recruiting heterochromatin protein 1 (HP1) to discrete regions of the genome, thereby regulating gene expression, chromatin packaging, and heterochromatin formation. Until now, little was known about the regulation of effector-histone mark interactions, and in particular, of the binding of HP1 to H3K9me3. Recently, we and others presented evidence that a "binary methylation-phosphorylation switch" mechanism controls the dynamic release of HP1 from H3K9me3 during the cell cycle: phosphorylation of histone H3 serine 10 (H3S10ph) occurs at the onset of mitosis, interferes with HP1-H3K9me3 interaction, and therefore, ejects HP1 from its binding site. Here, we discuss the biological function of HP1 release from chromatin during mitosis, consider implications why the cell controls HP1 binding by such a methylation-phosphorylation switching mechanism, and reflect on other cellular pathways where binary switching of HP1 might occur.

Original languageEnglish (US)
Pages (from-to)2842-2851
Number of pages10
JournalCell Cycle
Volume5
Issue number24
DOIs
StatePublished - Dec 15 2006

Keywords

  • Binary switch
  • Chromatin
  • Effector protein
  • HP1
  • Histone modification
  • Methylation
  • Phosphorylation

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

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