An expression screen reveals modulators of class II histone deacetylase phosphorylation

Shurong Chang, Svetlana Bezprozvannaya, Shijie Li, Eric N. Olson

Research output: Contribution to journalArticle

89 Citations (Scopus)

Abstract

Class II histone deacetylases (HDACs) repress transcription by associating with a variety of transcription factors and corepressors. Phosphorylation of a set of conserved serine residues in the N-terminal extensions of class II HDACs creates binding sites for 14-3-3 chaperone proteins, which trigger nuclear export of these HDACs, thereby derepressing specific target genes in a signal-dependent manner. To identify intracellular signaling pathways that control phosphorylation of HDAC5, a class II HDAC, we designed a eukaryotic cDNA expression screen in which a GAL4-dependent luciferase reporter was expressed with the DNA-binding domain of GAL4 fused to the N-terminal extension of HDAC5 and the VP16 transcription activation domain fused to 14-3-3. The transfection of COS cells with cDNA expression libraries results in activation of luciferase expression by cDNAs encoding HDAC5 kinases or modulators of such kinases that enable phosphorylated GAL4-HDAC5 to recruit 14-3-3-VP16 with consequent reconstitution of a functional transcriptional complex. Our results reveal a remarkable variety of signaling pathways that converge on the signal-responsive phosphorylation sites in HDACS, thereby enabling HDAC5 to connect extracellular signals to the genome.

Original languageEnglish (US)
Pages (from-to)8120-8125
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume102
Issue number23
DOIs
StatePublished - Jun 7 2005

Fingerprint

Histone Deacetylases
Phosphorylation
Luciferases
Phosphotransferases
Complementary DNA
14-3-3 Proteins
Co-Repressor Proteins
Cell Nucleus Active Transport
COS Cells
Gene Library
Serine
Transcriptional Activation
Transfection
Transcription Factors
Binding Sites
Genome
DNA
Genes

Keywords

  • Endothelial differentiation genes
  • Lysophosphatidic acid receptors
  • Rho signaling
  • Sphingosine-1 phosphate

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

An expression screen reveals modulators of class II histone deacetylase phosphorylation. / Chang, Shurong; Bezprozvannaya, Svetlana; Li, Shijie; Olson, Eric N.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 102, No. 23, 07.06.2005, p. 8120-8125.

Research output: Contribution to journalArticle

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