The COMPASS family of histone H3K4 methylases: Mechanisms of regulation in development and disease pathogenesis

Ali Shilatifard*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

529 Scopus citations

Abstract

The Saccharomyces cerevisiae Set1COMPASS was the first histone H3 lysine 4 (H3K4) methylase identified over 10 years ago. Since then, it has been demonstrated that Set1COMPASS and its enzymatic product, H3K4 methylation, is highly conserved across the evolutionary tree. Although there is only one COMPASS in yeast, Drosophila possesses three and humans bear six COMPASS family members, each capable of methylating H3K4 with nonredundant functions. In yeast, the histone H2B monoubiquitinase Rad6Bre1 is required for proper H3K4 and H3K79 trimethylations. The machineries involved in this process are also highly conserved from yeast to human. In this review, the process of histone H2B monoubiquitination-dependent and-independent histone H3K4 methylation as a mark of active transcription, enhancer signatures, and developmentally poised genes is discussed. The misregulation of histone H2B monoubiquitination and H3K4 methylation result in the pathogenesis of human diseases, including cancer. Recent findings in this regard are also examined.

Original languageEnglish (US)
Pages (from-to)65-95
Number of pages31
JournalAnnual review of biochemistry
Volume81
DOIs
StatePublished - Jul 2012

Keywords

  • MLL
  • Rad6Bre1
  • Set1
  • chromosomal translocations in leukemia
  • histone methylation
  • histone monoubiquitination

ASJC Scopus subject areas

  • Biochemistry

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