PMID- 20107518
OWN - NLM
STAT- MEDLINE
DCOM- 20100309
LR  - 20211020
IS  - 1553-7374 (Electronic)
IS  - 1553-7366 (Print)
IS  - 1553-7366 (Linking)
VI  - 6
IP  - 1
DP  - 2010 Jan 22
TI  - Histone deacetylases play a major role in the transcriptional regulation of the 
      Plasmodium falciparum life cycle.
PG  - e1000737
LID - 10.1371/journal.ppat.1000737 [doi]
LID - e1000737
AB  - The apparent paucity of molecular factors of transcriptional control in the 
      genomes of Plasmodium parasites raises many questions about the mechanisms of 
      life cycle regulation in these malaria parasites. Epigenetic regulation has been 
      suggested to play a major role in the stage specific gene expression during the 
      Plasmodium life cycle. To address some of these questions, we analyzed global 
      transcriptional responses of Plasmodium falciparum to a potent inhibitor of 
      histone deacetylase activities (HDAC). The inhibitor apicidin induced profound 
      transcriptional changes in multiple stages of the P. falciparum intraerythrocytic 
      developmental cycle (IDC) that were characterized by rapid activation and 
      repression of a large percentage of the genome. A major component of this 
      response was induction of genes that are otherwise suppressed during that 
      particular stage of the IDC or specific for the exo-erythrocytic stages. In the 
      schizont stage, apicidin induced hyperacetylation of histone lysine residues 
      H3K9, H4K8 and the tetra-acetyl H4 (H4Ac4) and demethylation of H3K4me3. 
      Interestingly, we observed overlapping patterns of chromosomal distributions 
      between H4K8Ac and H3K4me3 and between H3K9Ac and H4Ac4. There was a significant 
      but partial association between the apicidin-induced gene expression and histone 
      modifications, which included a number of stage specific transcription factors. 
      Taken together, inhibition of HDAC activities leads to dramatic de-regulation of 
      the IDC transcriptional cascade, which is a result of both disruption of histone 
      modifications and up-regulation of stage specific transcription factors. These 
      findings suggest an important role of histone modification and chromatin 
      remodeling in transcriptional regulation of the Plasmodium life cycle. This also 
      emphasizes the potential of P. falciparum HDACs as drug targets for malaria 
      chemotherapy.
FAU - Chaal, Balbir K
AU  - Chaal BK
AD  - School of Biological Sciences, Nanyang Technological University, Singapore.
FAU - Gupta, Archna P
AU  - Gupta AP
FAU - Wastuwidyaningtyas, Brigitta D
AU  - Wastuwidyaningtyas BD
FAU - Luah, Yen-Hoon
AU  - Luah YH
FAU - Bozdech, Zbynek
AU  - Bozdech Z
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100122
PL  - United States
TA  - PLoS Pathog
JT  - PLoS pathogens
JID - 101238921
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Peptides, Cyclic)
RN  - 0 (RNA, Messenger)
RN  - 0 (apicidin)
RN  - EC 3.5.1.98 (Histone Deacetylases)
SB  - IM
MH  - Enzyme Inhibitors/pharmacology
MH  - Gene Expression Regulation, Developmental/*physiology
MH  - Histone Deacetylases/*genetics
MH  - Immunoprecipitation
MH  - Oligonucleotide Array Sequence Analysis
MH  - Peptides, Cyclic/pharmacology
MH  - Plasmodium falciparum/*growth & development/*physiology
MH  - RNA, Messenger/biosynthesis
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - *Transcription, Genetic
PMC - PMC2809759
COIS- The authors have declared that no competing interests exist.
EDAT- 2010/01/29 06:00
MHDA- 2010/03/10 06:00
PMCR- 2010/01/22
CRDT- 2010/01/29 06:00
PHST- 2009/06/17 00:00 [received]
PHST- 2009/12/21 00:00 [accepted]
PHST- 2010/01/29 06:00 [entrez]
PHST- 2010/01/29 06:00 [pubmed]
PHST- 2010/03/10 06:00 [medline]
PHST- 2010/01/22 00:00 [pmc-release]
AID - 09-PLPA-RA-0980R3 [pii]
AID - 10.1371/journal.ppat.1000737 [doi]
PST - epublish
SO  - PLoS Pathog. 2010 Jan 22;6(1):e1000737. doi: 10.1371/journal.ppat.1000737.