PfGCN5-mediated histone H3 acetylation plays a key role in gene expression in Plasmodium falciparum

Long Cui, Jun Miao, Tetsuya Furuya, Xinyi Li, Xin Zhuan Su, Liwang Cui

Research output: Contribution to journalArticle

81 Citations (Scopus)

Abstract

Histone acetylation, regulated by the opposing actions of histone acetyltransferases (HATs) and deacetylases, is an important epigenetic mechanism in eukaryotic transcription. Although an acetyltransferase (PfGCN5) has been shown to preferentially acetylate histone H3 at K9 and K14 in Plasmodium falciparum, the scale of histone acetylation in the parasite genome and its role in transcriptional activation are essentially unknown. Using chromatin immunoprecipitation (ChIP) and DNA microarray, we mapped the global distribution of PfGCN5, histone H3K9 acetylation (H3K9ac) and trimethylation (H3K9m3) in the P. falciparum genome. While the chromosomal distributions of H3K9ac and PfGCN5 were similar, they are radically different from that of H3K9m3. In addition, there was a positive, though weak correlation between relative occupancy of H3K9ac on individual genes and the levels of gene expression, which was inversely proportional to the distance of array elements from the putative translational start codons. In contrast, H3K9m3 was negatively correlated with gene expression. Furthermore, detailed mapping of H3K9ac for selected genes using ChIP and real-time PCR in three erythrocytic stages detected stage-specific peak H3K9ac enrichment at the putative transcriptional initiation sites, corresponding to stage-specific expression of these genes. These data are consistent with H3K9ac and H3K9m3 as epigenetic markers of active and silent genes, respectively. We also showed that treatment with a PfGCN5 inhibitor led to reduced promoter H3K9ac and gene expression. Collectively, these results suggest that PfGCN5 is recruited to the promoter regions of genes to mediate histone acetylation and activate gene expression in P. falciparum.

Original languageEnglish (US)
Pages (from-to)1219-1227
Number of pages9
JournalEukaryotic Cell
Volume6
Issue number7
DOIs
StatePublished - Jul 1 2007

Fingerprint

Plasmodium falciparum
Acetylation
Histones
Gene Expression
Chromatin Immunoprecipitation
Epigenomics
Genes
Genome
Histone Acetyltransferases
Acetyltransferases
Histone Deacetylases
Initiator Codon
Oligonucleotide Array Sequence Analysis
Genetic Promoter Regions
Transcriptional Activation
Real-Time Polymerase Chain Reaction
Parasites

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Molecular Biology

Cite this

Cui, Long ; Miao, Jun ; Furuya, Tetsuya ; Li, Xinyi ; Su, Xin Zhuan ; Cui, Liwang. / PfGCN5-mediated histone H3 acetylation plays a key role in gene expression in Plasmodium falciparum. In: Eukaryotic Cell. 2007 ; Vol. 6, No. 7. pp. 1219-1227.
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PfGCN5-mediated histone H3 acetylation plays a key role in gene expression in Plasmodium falciparum. / Cui, Long; Miao, Jun; Furuya, Tetsuya; Li, Xinyi; Su, Xin Zhuan; Cui, Liwang.

In: Eukaryotic Cell, Vol. 6, No. 7, 01.07.2007, p. 1219-1227.

Research output: Contribution to journalArticle

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