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Histone H3K9 acetylation level modulates gene expression and may affect parasite growth in human malaria parasite Plasmodium falciparum

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dc.contributor.author Srivastava, Sandeep
dc.contributor.author Bhowmick, Krishanu
dc.contributor.author Chatterjee, Snehajyoti
dc.contributor.author Basha, Jeelan
dc.contributor.author Kundu, Tapas Kumar
dc.contributor.author Dhar, Suman K.
dc.date.accessioned 2017-02-17T05:09:16Z
dc.date.available 2017-02-17T05:09:16Z
dc.date.issued 2014
dc.identifier.citation Srivastava, 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.13067 en_US
dc.identifier.citation FEBS Journal en_US
dc.identifier.citation 281 en_US
dc.identifier.citation 23 en_US
dc.identifier.issn 1742-464X
dc.identifier.uri https://libjncir.jncasr.ac.in/xmlui/10572/2333
dc.description Restricted Access en_US
dc.description.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. en_US
dc.description.uri 1742-4658 en_US
dc.description.uri http://dx.doi.org/10.1111/febs.13067 en_US
dc.language.iso English en_US
dc.publisher Wiley-Blackwell en_US
dc.rights @Wiley-Blackwell, 2014 en_US
dc.subject Biochemistry & Molecular Biology en_US
dc.subject Embelin en_US
dc.subject Epigenetics en_US
dc.subject Gcn5 en_US
dc.subject H3K9Ac en_US
dc.subject Plasmodium Falciparum en_US
dc.subject Mutually Exclusive Expression en_US
dc.subject Antigenic Variation en_US
dc.subject Virulence Genes en_US
dc.subject Intraerythrocytic Development en_US
dc.subject Acetyltransferase Complexes en_US
dc.subject Nuclear-Envelope en_US
dc.subject Chromatin en_US
dc.subject Erythrocytes en_US
dc.subject Organization en_US
dc.subject Genome en_US
dc.title Histone H3K9 acetylation level modulates gene expression and may affect parasite growth in human malaria parasite Plasmodium falciparum en_US
dc.type Article en_US


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