Discovery of a new predominant cytosine DNA modification that is linked to gene expression in malaria parasites
DNA cytosine modifications are key epigenetic regulators of cellular processes in mammalian cells, with their misregulation leading to varied disease states. In the human malaria parasite Plasmodium falciparum, a unicellular eukaryotic pathogen, little is known about the predominant cytosine modific...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Oxford University Press (OUP)
2020
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| Online Access: | https://hdl.handle.net/1721.1/126273 |
| _version_ | 1811088649189588992 |
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| author | Hammam, Elie Ananda, Guruprasad Sinha, Ameya Scheidig-Benatar, Christine Bohec, Mylene Preiser, Peter R Dedon, Peter C Scherf, Artur Vembar, Shruthi S |
| author2 | Massachusetts Institute of Technology. Department of Biological Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Biological Engineering Hammam, Elie Ananda, Guruprasad Sinha, Ameya Scheidig-Benatar, Christine Bohec, Mylene Preiser, Peter R Dedon, Peter C Scherf, Artur Vembar, Shruthi S |
| author_sort | Hammam, Elie |
| collection | MIT |
| description | DNA cytosine modifications are key epigenetic regulators of cellular processes in mammalian cells, with their misregulation leading to varied disease states. In the human malaria parasite Plasmodium falciparum, a unicellular eukaryotic pathogen, little is known about the predominant cytosine modifications, cytosine methylation (5mC) and hydroxymethylation (5hmC). Here, we report the first identification of a hydroxymethylcytosine-like (5hmC-like) modification in P. falciparum asexual blood stages using a suite of biochemical methods. In contrast to mammalian cells, we report 5hmC-like levels in the P. falciparum genome of 0.2-0.4%, which are significantly higher than the methylated cytosine (mC) levels of 0.01-0.05%. Immunoprecipitation of hydroxymethylated DNA followed by next generation sequencing (hmeDIP-seq) revealed that 5hmC-like modifications are enriched in gene bodies with minimal dynamic changes during asexual development. Moreover, levels of the 5hmC-like base in gene bodies positively correlated to transcript levels, with more than 2000 genes stably marked with this modification throughout asexual development. Our work highlights the existence of a new predominant cytosine DNA modification pathway in P. falciparum and opens up exciting avenues for gene regulation research and the development of antimalarials. |
| first_indexed | 2024-09-23T14:05:20Z |
| format | Article |
| id | mit-1721.1/126273 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T14:05:20Z |
| publishDate | 2020 |
| publisher | Oxford University Press (OUP) |
| record_format | dspace |
| spelling | mit-1721.1/1262732022-09-28T18:20:20Z Discovery of a new predominant cytosine DNA modification that is linked to gene expression in malaria parasites Hammam, Elie Ananda, Guruprasad Sinha, Ameya Scheidig-Benatar, Christine Bohec, Mylene Preiser, Peter R Dedon, Peter C Scherf, Artur Vembar, Shruthi S Massachusetts Institute of Technology. Department of Biological Engineering DNA cytosine modifications are key epigenetic regulators of cellular processes in mammalian cells, with their misregulation leading to varied disease states. In the human malaria parasite Plasmodium falciparum, a unicellular eukaryotic pathogen, little is known about the predominant cytosine modifications, cytosine methylation (5mC) and hydroxymethylation (5hmC). Here, we report the first identification of a hydroxymethylcytosine-like (5hmC-like) modification in P. falciparum asexual blood stages using a suite of biochemical methods. In contrast to mammalian cells, we report 5hmC-like levels in the P. falciparum genome of 0.2-0.4%, which are significantly higher than the methylated cytosine (mC) levels of 0.01-0.05%. Immunoprecipitation of hydroxymethylated DNA followed by next generation sequencing (hmeDIP-seq) revealed that 5hmC-like modifications are enriched in gene bodies with minimal dynamic changes during asexual development. Moreover, levels of the 5hmC-like base in gene bodies positively correlated to transcript levels, with more than 2000 genes stably marked with this modification throughout asexual development. Our work highlights the existence of a new predominant cytosine DNA modification pathway in P. falciparum and opens up exciting avenues for gene regulation research and the development of antimalarials. 2020-07-21T14:46:07Z 2020-07-21T14:46:07Z 2019-11 2019-10 2020-03-05T17:41:30Z Article http://purl.org/eprint/type/JournalArticle 0305-1048 1362-4962 https://hdl.handle.net/1721.1/126273 Hammam, Ellie et al. "Discovery of a new predominant cytosine DNA modification that is linked to gene expression in malaria parasites." Nucleic Acids Research 48, 1 (November 2019): 184–199 © 2019 The Author(s) en http://dx.doi.org/10.1093/nar/gkz1093 Nucleic Acids Research Creative Commons Attribution NonCommercial License 4.0 https://creativecommons.org/licenses/by-nc/4.0/ application/pdf Oxford University Press (OUP) Nucleic Acids Research |
| spellingShingle | Hammam, Elie Ananda, Guruprasad Sinha, Ameya Scheidig-Benatar, Christine Bohec, Mylene Preiser, Peter R Dedon, Peter C Scherf, Artur Vembar, Shruthi S Discovery of a new predominant cytosine DNA modification that is linked to gene expression in malaria parasites |
| title | Discovery of a new predominant cytosine DNA modification that is linked to gene expression in malaria parasites |
| title_full | Discovery of a new predominant cytosine DNA modification that is linked to gene expression in malaria parasites |
| title_fullStr | Discovery of a new predominant cytosine DNA modification that is linked to gene expression in malaria parasites |
| title_full_unstemmed | Discovery of a new predominant cytosine DNA modification that is linked to gene expression in malaria parasites |
| title_short | Discovery of a new predominant cytosine DNA modification that is linked to gene expression in malaria parasites |
| title_sort | discovery of a new predominant cytosine dna modification that is linked to gene expression in malaria parasites |
| url | https://hdl.handle.net/1721.1/126273 |
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