Nuclear import and activity of histone deacetylase in Xenopus oocytes is regulated by phosphorylation

DA Smillie, AJ Llinas, JTP Ryan, Graham Duncan Kemp, John Sommerville

Research output: Contribution to journalArticlepeer-review

26 Citations (Scopus)

Abstract

Most of the histone deacetylase (HDAC) activity detected in oocytes; and early embryos of Xenopus can be accounted for by the presence of a protein complex that contains the maternal HDACm protein. This complex appears to fulfil the conditions required of a 'deposition' histone deacetylase, its primary function being to deacetylate the core histones incorporated into newly-synthesized chromatin during the rapid cell cycles leading up to blastula. A major event in the assembly and accumulation of the HDAC complex is the translocation of the HDACm protein into the germinal vesicle during oogenesis. Here we examine the features of HDACm that are responsible for its nuclear uptake and enzyme activity, identifying the charged C-terminal domain as a target for modification by phosphorylation. Whereas, one phosphorylation site lying within the putative nuclear localization signal, T445, is required for efficient nuclear import of a GST-carboxy-tail fusion, two others, S421 and S423, appear to effect release from the import receptors. Although overexpression of recombinant HDACm in oocytes leads to premature condensation of endogenous chromatin, this effect is abrogated in vivo by mutation of S421A and S423A. Thus, both translocation and activity of HDACm appear to be regulated by specific phosphorylation events. These results have implications for techniques involving the transfer of somatic nuclei into enucleated oocytes.

Original languageEnglish
Pages (from-to)1857 - 1866
Number of pages10
JournalJournal of Cell Science
Volume117
Issue number9
DOIs
Publication statusPublished - 1 Apr 2004

Keywords

  • histones/chromatin
  • protein phosphorylation
  • nuclear import
  • PROTEIN-KINASE CK2
  • NUCLEOCYTOPLASMIC TRANSPORT
  • ACETYLATION
  • CHROMATIN
  • LAEVIS
  • COMPLEXES
  • TRANSCRIPTION
  • NUCLEOPLASMIN
  • RECOGNITION
  • FAMILY

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