Dynamic epigenetic regulation of gene expression during the life cycle of malaria parasite Plasmodium falciparum

Epigenetic mechanisms are emerging as one of the major factors of the dynamics of gene expression in the human malaria parasite, Plasmodium falciparum. To elucidate the role of chromatin remodeling in transcriptional regulation associated with the progression of the P. falciparum intraerythrocytic d...

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Main Authors: Chin, Wai Hoe, Zhu, Lei, Mok, Sachel, Luah, Yen-Hoon, Lim, Eng-How, Bozdech, Zbynek, Gupta, Archna P.
Other Authors: Deitsch, Kirk
Format: Article
Language:English
Published: 2013
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Online Access:https://hdl.handle.net/10356/101192
http://hdl.handle.net/10220/18291
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Institution: Nanyang Technological University
Language: English
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spelling sg-ntu-dr.10356-1011922023-02-28T17:00:27Z Dynamic epigenetic regulation of gene expression during the life cycle of malaria parasite Plasmodium falciparum Chin, Wai Hoe Zhu, Lei Mok, Sachel Luah, Yen-Hoon Lim, Eng-How Bozdech, Zbynek Gupta, Archna P. Deitsch, Kirk School of Biological Sciences DRNTU::Science::Biological sciences Epigenetic mechanisms are emerging as one of the major factors of the dynamics of gene expression in the human malaria parasite, Plasmodium falciparum. To elucidate the role of chromatin remodeling in transcriptional regulation associated with the progression of the P. falciparum intraerythrocytic development cycle (IDC), we mapped the temporal pattern of chromosomal association with histone H3 and H4 modifications using ChIP-on-chip. Here, we have generated a broad integrative epigenomic map of twelve histone modifications during the P. falciparum IDC including H4K5ac, H4K8ac, H4K12ac, H4K16ac, H3K9ac, H3K14ac, H3K56ac, H4K20me1, H4K20me3, H3K4me3, H3K79me3 and H4R3me2. While some modifications were found to be associated with the vast majority of the genome and their occupancy was constant, others showed more specific and highly dynamic distribution. Importantly, eight modifications displaying tight correlations with transcript levels showed differential affinity to distinct genomic regions with H4K8ac occupying predominantly promoter regions while others occurred at the 5′ ends of coding sequences. The promoter occupancy of H4K8ac remained unchanged when ectopically inserted at a different locus, indicating the presence of specific DNA elements that recruit histone modifying enzymes regardless of their broad chromatin environment. In addition, we showed the presence of multivalent domains on the genome carrying more than one histone mark, highlighting the importance of combinatorial effects on transcription. Overall, our work portrays a substantial association between chromosomal locations of various epigenetic markers, transcriptional activity and global stage-specific transitions in the epigenome. NMRC (Natl Medical Research Council, S’pore) Published version 2013-12-17T09:17:35Z 2019-12-06T20:35:02Z 2013-12-17T09:17:35Z 2019-12-06T20:35:02Z 2013 2013 Journal Article Gupta, A. P., Chin, W. H., Zhu, L., Mok, S., Luah, Y.-H., Lim, E.-H., et al. (2013). Dynamic epigenetic regulation of gene expression during the life cycle of malaria parasite plasmodium falciparum. PLoS pathogens, 9(2), e1003170-. 1553-7366 https://hdl.handle.net/10356/101192 http://hdl.handle.net/10220/18291 10.1371/journal.ppat.1003170 23468622 en PLoS pathogens © 2013 The Author(s). This paper was published in PLoS Pathogens and is made available as an electronic reprint (preprint) with permission of The Author(s). The paper can be found at the following official DOI: http://dx.doi.org/10.1371/journal.ppat.1003170.  One print or electronic copy may be made for personal use only. Systematic or multiple reproduction, distribution to multiple locations via electronic or other means, duplication of any material in this paper for a fee or for commercial purposes, or modification of the content of the paper is prohibited and is subject to penalties under law. application/pdf
institution Nanyang Technological University
building NTU Library
continent Asia
country Singapore
Singapore
content_provider NTU Library
collection DR-NTU
language English
topic DRNTU::Science::Biological sciences
spellingShingle DRNTU::Science::Biological sciences
Chin, Wai Hoe
Zhu, Lei
Mok, Sachel
Luah, Yen-Hoon
Lim, Eng-How
Bozdech, Zbynek
Gupta, Archna P.
Dynamic epigenetic regulation of gene expression during the life cycle of malaria parasite Plasmodium falciparum
description Epigenetic mechanisms are emerging as one of the major factors of the dynamics of gene expression in the human malaria parasite, Plasmodium falciparum. To elucidate the role of chromatin remodeling in transcriptional regulation associated with the progression of the P. falciparum intraerythrocytic development cycle (IDC), we mapped the temporal pattern of chromosomal association with histone H3 and H4 modifications using ChIP-on-chip. Here, we have generated a broad integrative epigenomic map of twelve histone modifications during the P. falciparum IDC including H4K5ac, H4K8ac, H4K12ac, H4K16ac, H3K9ac, H3K14ac, H3K56ac, H4K20me1, H4K20me3, H3K4me3, H3K79me3 and H4R3me2. While some modifications were found to be associated with the vast majority of the genome and their occupancy was constant, others showed more specific and highly dynamic distribution. Importantly, eight modifications displaying tight correlations with transcript levels showed differential affinity to distinct genomic regions with H4K8ac occupying predominantly promoter regions while others occurred at the 5′ ends of coding sequences. The promoter occupancy of H4K8ac remained unchanged when ectopically inserted at a different locus, indicating the presence of specific DNA elements that recruit histone modifying enzymes regardless of their broad chromatin environment. In addition, we showed the presence of multivalent domains on the genome carrying more than one histone mark, highlighting the importance of combinatorial effects on transcription. Overall, our work portrays a substantial association between chromosomal locations of various epigenetic markers, transcriptional activity and global stage-specific transitions in the epigenome.
author2 Deitsch, Kirk
author_facet Deitsch, Kirk
Chin, Wai Hoe
Zhu, Lei
Mok, Sachel
Luah, Yen-Hoon
Lim, Eng-How
Bozdech, Zbynek
Gupta, Archna P.
format Article
author Chin, Wai Hoe
Zhu, Lei
Mok, Sachel
Luah, Yen-Hoon
Lim, Eng-How
Bozdech, Zbynek
Gupta, Archna P.
author_sort Chin, Wai Hoe
title Dynamic epigenetic regulation of gene expression during the life cycle of malaria parasite Plasmodium falciparum
title_short Dynamic epigenetic regulation of gene expression during the life cycle of malaria parasite Plasmodium falciparum
title_full Dynamic epigenetic regulation of gene expression during the life cycle of malaria parasite Plasmodium falciparum
title_fullStr Dynamic epigenetic regulation of gene expression during the life cycle of malaria parasite Plasmodium falciparum
title_full_unstemmed Dynamic epigenetic regulation of gene expression during the life cycle of malaria parasite Plasmodium falciparum
title_sort dynamic epigenetic regulation of gene expression during the life cycle of malaria parasite plasmodium falciparum
publishDate 2013
url https://hdl.handle.net/10356/101192
http://hdl.handle.net/10220/18291
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