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dc.contributor.authorSrivastava, Sandeep
dc.contributor.authorBhowmick, Krishanu
dc.contributor.authorChatterjee, Snehajyoti
dc.contributor.authorBasha, Jeelan
dc.contributor.authorKundu, Tapas Kumar
dc.contributor.authorDhar, Suman K.
dc.date.accessioned2017-02-17T05:09:16Z-
dc.date.available2017-02-17T05:09:16Z-
dc.date.issued2014
dc.identifier.citationSrivastava, S; Bhowmick, K; Chatterjee, S; Basha, J; Kundu, TK; Dhar, SK, Histone H3K9 acetylation level modulates gene expression and may affect parasite growth in human malaria parasite Plasmodium falciparum. Febs Journal 2014, 281 (23) 5265-5278, http://dx.doi.org/10.1111/febs.13067en_US
dc.identifier.citationFEBS Journalen_US
dc.identifier.citation281en_US
dc.identifier.citation23en_US
dc.identifier.issn1742-464X
dc.identifier.urihttp://hdl.handle.net/10572/2333-
dc.descriptionRestricted Accessen_US
dc.description.abstractThree-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.en_US
dc.description.uri1742-4658en_US
dc.description.urihttp://dx.doi.org/10.1111/febs.13067en_US
dc.language.isoEnglishen_US
dc.publisherWiley-Blackwellen_US
dc.rights@Wiley-Blackwell, 2014en_US
dc.subjectBiochemistry & Molecular Biologyen_US
dc.subjectEmbelinen_US
dc.subjectEpigeneticsen_US
dc.subjectGcn5en_US
dc.subjectH3K9Acen_US
dc.subjectPlasmodium Falciparumen_US
dc.subjectMutually Exclusive Expressionen_US
dc.subjectAntigenic Variationen_US
dc.subjectVirulence Genesen_US
dc.subjectIntraerythrocytic Developmenten_US
dc.subjectAcetyltransferase Complexesen_US
dc.subjectNuclear-Envelopeen_US
dc.subjectChromatinen_US
dc.subjectErythrocytesen_US
dc.subjectOrganizationen_US
dc.subjectGenomeen_US
dc.titleHistone H3K9 acetylation level modulates gene expression and may affect parasite growth in human malaria parasite Plasmodium falciparumen_US
dc.typeArticleen_US
Appears in Collections:Research Papers (Tapas K. Kundu)

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