Heterochromatin Protein 1a Stimulates Histone H3 Lysine 36 Demethylation by the Drosophila KDM4A Demethylase

Chia Hui Lin, Bing Li, Selene Swanson, Ying Zhang, Laurence Florens, Michael P. Washburn, Susan M. Abmayr, Jerry L. Workman

Research output: Contribution to journalArticle

77 Scopus citations

Abstract

Recent discoveries of histone demethylases demonstrate that histone methylation is reversible. However, mechanisms governing the targeting and regulation of histone demethylation remain elusive. Here we report that a Drosophila melanogaster JmjC domain-containing protein, dKDM4A, is a histone H3K36 demethylase. dKDM4A specifically demethylates H3K36me2 and H3K36me3 both in vitro and in vivo. Affinity purification and mass spectrometry analysis revealed that heterochromatin protein 1a (HP1a) associates with dKDMA4A. We found that the chromo shadow domain of HP1a and a HP1-interacting motif of dKDM4A are responsible for this interaction. HP1a stimulates the histone H3K36 demethylation activity of dKDM4A, and this stimulation depends on the H3K9me-binding motif of HP1a. Finally, we provide in vivo evidence suggesting that HP1a and dKDM4A interact with each other and that loss of HP1a leads to an increased level of histone H3K36me3. Collectively, these results suggest a function of HP1a in transcription facilitating H3K36 demethylation at transcribed and/or heterochromatin regions.

Original languageEnglish (US)
Pages (from-to)696-706
Number of pages11
JournalMolecular cell
Volume32
Issue number5
DOIs
StatePublished - Dec 5 2008

Keywords

  • DNA

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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    Lin, C. H., Li, B., Swanson, S., Zhang, Y., Florens, L., Washburn, M. P., Abmayr, S. M., & Workman, J. L. (2008). Heterochromatin Protein 1a Stimulates Histone H3 Lysine 36 Demethylation by the Drosophila KDM4A Demethylase. Molecular cell, 32(5), 696-706. https://doi.org/10.1016/j.molcel.2008.11.008