The nuclear-envelope protein and transcriptional repressor LAP2β interacts with HDAC3 at the nuclear periphery, and induces histone H4 deacetylation

Raz Somech, Sigal Shaklai, Orit Geller, Ninette Amariglio, Amos J. Simon, Gideon Rechavi, Einav Nili Gal-Yam

Research output: Contribution to journalArticle

137 Citations (Scopus)

Abstract

Nuclear-envelope proteins have been implicated in diverse and fundamental cell functions, among them transcriptional regulation. Gene expression at the territory of the nuclear periphery is known to be repressed by epigenetic modifications such as histone deacetylation and methylation. However, the mechanism by which nuclear-envelope proteins are involved in such modifications is still obscure. We have previously shown that LAP2β, an integral nuclear-envelope protein that contains the chromatin-binding LEM domain, was able to repress the transcriptional activity of the E2F5-DP3 heterodimer. Here, we show that LAP2β's repressive activity is more general, encompassing various E2F members as well as other transcription factors such as p53 and NF-κB. We further show that LAP2β interacts at the nuclear envelope with HDAC3, a class-I histone deacetylase, and that TSA (an HDAC inhibitor) abrogates LAP2β's repressive activity. Finally, we show that LAP2β is capable of inducing histone-H4 deacetylation. Our data provide evidence for the existence of a previously unknown repressive complex, composed of an integral nuclear membrane protein and a histone modifier, at the nuclear periphery.

Original languageEnglish (US)
Pages (from-to)4017-4025
Number of pages9
JournalJournal of cell science
Volume118
Issue number17
DOIs
StatePublished - Sep 1 2005

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Nuclear Envelope
Nuclear Proteins
Histones
Histone Deacetylase Inhibitors
Histone Deacetylases
Epigenomics
Methylation
Chromatin
Membrane Proteins
Transcription Factors
Gene Expression

Keywords

  • Chromatin architecture
  • HDAC3
  • Histone modification
  • LAP2β
  • Nuclear envelope
  • Transcriptional repression

ASJC Scopus subject areas

  • Cell Biology

Cite this

The nuclear-envelope protein and transcriptional repressor LAP2β interacts with HDAC3 at the nuclear periphery, and induces histone H4 deacetylation. / Somech, Raz; Shaklai, Sigal; Geller, Orit; Amariglio, Ninette; Simon, Amos J.; Rechavi, Gideon; Gal-Yam, Einav Nili.

In: Journal of cell science, Vol. 118, No. 17, 01.09.2005, p. 4017-4025.

Research output: Contribution to journalArticle

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