Journal article
Histone H3K9 acetylation level modulates gene expression and may affect parasite growth in human malaria parasite Plasmodium falciparum
The FEBS journal, Vol.281(23), pp.5265-5278
12/01/2014
DOI: 10.1111/febs.13067
PMID: 25252094
Abstract
Three-dimensional positioning of the nuclear genome plays an important role in the epigenetic regulation of genes. Although nucleographic domain compartmentalization in the regulation of epigenetic state and gene expression is well established in higher organisms, it remains poorly understood in the pathogenic parasite Plasmodium falciparum. In the present study, we report that two histone tail modifications, H3K9Ac and H3K14Ac, are differentially distributed in the parasite nucleus. We find colocalization of active gene promoters such as Tu1 (tubulin-1 expressed in the asexual stages) with H3K9Ac marks at the nuclear periphery. By contrast, asexual stage inactive gene promoters such as Pfg27 (gametocyte marker) and Pfs28 (ookinete marker) occupy H3K9Ac devoid zones at the nuclear periphery. The histone H3K9 is predominantly acetylated by the PCAF/GCN5 class of lysine acetyltransferases, which is well characterized in the parasite. Interestingly, embelin, a specific inhibitor of PCAF/GCN5 family histone acetyltransferase, selectively decreases total H3K9Ac acetylation levels (but not H3K14Ac levels) around the var gene promoters, leading to the downregulation of var gene expression, suggesting interplay among histone acetylation status, as well as subnuclear compartmentalization of different genes and their activation in the parasites. Finally, we found that embelin inhibited parasitic growth at the low micromolar range, raising the possibility of using histone acetyltransferases as a target for antimalarial therapy.
Details
- Title: Subtitle
- Histone H3K9 acetylation level modulates gene expression and may affect parasite growth in human malaria parasite Plasmodium falciparum
- Creators
- Sandeep Srivastava - Jawaharlal Nehru UniversityKrishanu Bhowmick - Jawaharlal Nehru UniversitySnehajyoti Chatterjee - Jawaharlal Nehru Centre for Advanced Scientific ResearchJeelan Basha - Jawaharlal Nehru Centre for Advanced Scientific ResearchTapas K. Kundu - Jawaharlal Nehru Centre for Advanced Scientific ResearchSuman K. Dhar - Jawaharlal Nehru University
- Resource Type
- Journal article
- Publication Details
- The FEBS journal, Vol.281(23), pp.5265-5278
- DOI
- 10.1111/febs.13067
- PMID
- 25252094
- NLM abbreviation
- FEBS J
- ISSN
- 1742-464X
- eISSN
- 1742-4658
- Publisher
- Wiley
- Number of pages
- 14
- Grant note
- DST-PURSE UGC-SAP; University Grants Commission, India Sir J. C. Bose National Fellowship, Department of Science & Technology, Govt of India JNCASR, Bangalore, India DBT-BUILDER programme in Chemical Biology ICMR; Indian Council of Medical Research (ICMR) CSIR, India; Council of Scientific & Industrial Research (CSIR) - India DST, India; Department of Science & Technology (India) National Biosciences Award for Career Development (Department of Biotechnology) Centre of Excellence (CoE) Grant (Department of Biotechnology) Swarnajayanti Fellowship (Department of Science and Technology) BT/01/CEIB/10/111/01 / Department of Biotechnology, Govt of India; Department of Biotechnology (DBT) India
- Language
- English
- Date published
- 12/01/2014
- Academic Unit
- Iowa Neuroscience Institute; Neuroscience and Pharmacology
- Record Identifier
- 9984303744902771
Metrics
5 Record Views