Histone 4 lysine 8 acetylation regulates proliferation and host–pathogen interaction in Plasmodium falciparum
Background: The dynamics of histone modifications in Plasmodium falciparum indicates the existence of unique mechanisms that link epigenetic factors with transcription. Here, we studied the impact of acetylated histone code on transcriptional regulation during the intraerythrocytic developmental cyc...
| Main Authors: | , , , , , |
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| Format: | Journal Article |
| Language: | English |
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2018
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| Online Access: | https://hdl.handle.net/10356/81066 http://hdl.handle.net/10220/46610 |
| _version_ | 1811677332687028224 |
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| author | Gupta, Archana P. Zhu, Lei Tripathi, Jaishree Kucharski, Michal Patra, Alok Bozdech, Zbynek |
| author2 | School of Biological Sciences |
| author_facet | School of Biological Sciences Gupta, Archana P. Zhu, Lei Tripathi, Jaishree Kucharski, Michal Patra, Alok Bozdech, Zbynek |
| author_sort | Gupta, Archana P. |
| collection | NTU |
| description | Background: The dynamics of histone modifications in Plasmodium falciparum indicates the existence of unique mechanisms that link epigenetic factors with transcription. Here, we studied the impact of acetylated histone code on transcriptional regulation during the intraerythrocytic developmental cycle (IDC) of P. falciparum. Results: Using a dominant-negative transgenic approach, we showed that acetylations of histone H4 play a direct role in transcription. Specifically, these histone modifications mediate an inverse transcriptional relationship between the factors of cell proliferation and host–parasite interaction. Out of the four H4 acetylations, H4K8ac is likely the rate-limiting, regulatory step, which modulates the overall dynamics of H4 posttranslational modifications. H4K8ac exhibits maximum responsiveness to HDAC inhibitors and has a highly dynamic distribution pattern along the genome of P. falciparum during the IDC. Moreover, H4K8ac functions mainly in the euchromatin where its occupancy shifts from intergenic regions located upstream of 5′ end of open reading frame into the protein coding regions. This shift is directly or indirectly associated with transcriptional activities at the corresponding genes. H4K8ac is also active in the heterochromatin where it stimulates expression of the main antigenic gene family (var) by its presence in the promoter region. Conclusions: Overall, we demonstrate that H4K8ac is a potential major regulator of chromatin-linked transcriptional changes during P. falciparum life cycle which is associated not only with euchromatin but also with heterochromatin environment. This is potentially a highly significant finding that suggests a regulatory connection between growth and parasite–host interaction both of which play a major role in malaria parasite virulence. |
| first_indexed | 2024-10-01T02:35:41Z |
| format | Journal Article |
| id | ntu-10356/81066 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T02:35:41Z |
| publishDate | 2018 |
| record_format | dspace |
| spelling | ntu-10356/810662023-02-28T16:58:01Z Histone 4 lysine 8 acetylation regulates proliferation and host–pathogen interaction in Plasmodium falciparum Gupta, Archana P. Zhu, Lei Tripathi, Jaishree Kucharski, Michal Patra, Alok Bozdech, Zbynek School of Biological Sciences DRNTU::Science::Biological sciences P. falciparum H4K8ac Background: The dynamics of histone modifications in Plasmodium falciparum indicates the existence of unique mechanisms that link epigenetic factors with transcription. Here, we studied the impact of acetylated histone code on transcriptional regulation during the intraerythrocytic developmental cycle (IDC) of P. falciparum. Results: Using a dominant-negative transgenic approach, we showed that acetylations of histone H4 play a direct role in transcription. Specifically, these histone modifications mediate an inverse transcriptional relationship between the factors of cell proliferation and host–parasite interaction. Out of the four H4 acetylations, H4K8ac is likely the rate-limiting, regulatory step, which modulates the overall dynamics of H4 posttranslational modifications. H4K8ac exhibits maximum responsiveness to HDAC inhibitors and has a highly dynamic distribution pattern along the genome of P. falciparum during the IDC. Moreover, H4K8ac functions mainly in the euchromatin where its occupancy shifts from intergenic regions located upstream of 5′ end of open reading frame into the protein coding regions. This shift is directly or indirectly associated with transcriptional activities at the corresponding genes. H4K8ac is also active in the heterochromatin where it stimulates expression of the main antigenic gene family (var) by its presence in the promoter region. Conclusions: Overall, we demonstrate that H4K8ac is a potential major regulator of chromatin-linked transcriptional changes during P. falciparum life cycle which is associated not only with euchromatin but also with heterochromatin environment. This is potentially a highly significant finding that suggests a regulatory connection between growth and parasite–host interaction both of which play a major role in malaria parasite virulence. Published version 2018-11-09T03:41:59Z 2019-12-06T14:20:42Z 2018-11-09T03:41:59Z 2019-12-06T14:20:42Z 2017 Journal Article Gupta, A. P., Zhu, L., Tripathi, J., Kucharski, M., Patra, A., & Bozdech, Z. (2017). Histone 4 lysine 8 acetylation regulates proliferation and host–pathogen interaction in Plasmodium falciparum. Epigenetics & Chromatin, 10, 40-. doi:10.1186/s13072-017-0147-z 1756-8935 https://hdl.handle.net/10356/81066 http://hdl.handle.net/10220/46610 10.1186/s13072-017-0147-z en Epigenetics & Chromatin © 2017 The Author(s). This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. 17 p. application/pdf |
| spellingShingle | DRNTU::Science::Biological sciences P. falciparum H4K8ac Gupta, Archana P. Zhu, Lei Tripathi, Jaishree Kucharski, Michal Patra, Alok Bozdech, Zbynek Histone 4 lysine 8 acetylation regulates proliferation and host–pathogen interaction in Plasmodium falciparum |
| title | Histone 4 lysine 8 acetylation regulates proliferation and host–pathogen interaction in Plasmodium falciparum |
| title_full | Histone 4 lysine 8 acetylation regulates proliferation and host–pathogen interaction in Plasmodium falciparum |
| title_fullStr | Histone 4 lysine 8 acetylation regulates proliferation and host–pathogen interaction in Plasmodium falciparum |
| title_full_unstemmed | Histone 4 lysine 8 acetylation regulates proliferation and host–pathogen interaction in Plasmodium falciparum |
| title_short | Histone 4 lysine 8 acetylation regulates proliferation and host–pathogen interaction in Plasmodium falciparum |
| title_sort | histone 4 lysine 8 acetylation regulates proliferation and host pathogen interaction in plasmodium falciparum |
| topic | DRNTU::Science::Biological sciences P. falciparum H4K8ac |
| url | https://hdl.handle.net/10356/81066 http://hdl.handle.net/10220/46610 |
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