HP1 recruits activity-dependent neuroprotective protein to H3K9me3 marked pericentromeric heterochromatin for silencing of major satellite repeats

Kerstin Mosch, Henriette Franz, Szabolcs Soeroes, Prim B Singh, Wolfgang Fischle

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

H3 lysine 9 trimethylation (H3K9me3) is a histone posttranslational modification (PTM) that has emerged as hallmark of pericentromeric heterochromatin. This constitutive chromatin domain is composed of repetitive DNA elements, whose transcription is differentially regulated. Mammalian cells contain three HP1 proteins, HP1α, HP1β and HP1γ These have been shown to bind to H3K9me3 and are thought to mediate the effects of this histone PTM. However, the mechanisms of HP1 chromatin regulation and the exact functional role at pericentromeric heterochromatin are still unclear. Here, we identify activity-dependent neuroprotective protein (ADNP) as an H3K9me3 associated factor. We show that ADNP does not bind H3K9me3 directly, but that interaction is mediated by all three HP1 isoforms in vitro. However, in cells ADNP localization to areas of pericentromeric heterochromatin is only dependent on HP1α and HP1β. Besides a PGVLL sequence patch we uncovered an ARKS motif within the ADNP homeodomain involved in HP1 dependent H3K9me3 association and localization to pericentromeric heterochromatin. While knockdown of ADNP had no effect on HP1 distribution and heterochromatic histone and DNA modifications, we found ADNP silencing major satellite repeats. Our results identify a novel factor in the translation of H3K9me3 at pericentromeric heterochromatin that regulates transcription.

Original languageEnglish
Pages (from-to)e15894
JournalPLoS One
Volume6
Issue number1
DOIs
Publication statusPublished - Jan 18 2011

Keywords

  • Animals
  • Cell Line
  • Chromosomal Proteins, Non-Histone
  • DNA, Satellite
  • Gene Expression Regulation
  • Gene Silencing
  • Heterochromatin
  • Histones
  • Homeodomain Proteins
  • Humans
  • Mice
  • Nerve Tissue Proteins
  • Protein Biosynthesis
  • Protein Transport
  • Repetitive Sequences, Nucleic Acid
  • Transcription, Genetic
  • Journal Article
  • Research Support, Non-U.S. Gov't

Fingerprint Dive into the research topics of 'HP1 recruits activity-dependent neuroprotective protein to H3K9me3 marked pericentromeric heterochromatin for silencing of major satellite repeats'. Together they form a unique fingerprint.

  • Cite this