Genome-wide analysis in Plasmodium falciparum reveals early and late phases of RNA polymerase II occupancy during the infectious cycle

Background: Over the course of its intraerythrocytic developmental cycle (IDC), the malaria parasite Plasmodium falciparum tightly orchestrates the rise and fall of transcript levels for hundreds of genes. Considerable debate has focused on the relative importance of transcriptional versus post-tr...

Full description

Saved in:
Bibliographic Details
Main Authors: Rai, Ragini, Zhu, Lei, Chen, Haifen, Gupta, Archana Patkar, Sze, Siu Kwan, Zheng, Jie, Ruedl, Christiane, Bozdech, Zbynek, Featherstone, Mark
Other Authors: School of Computer Engineering
Format: Article
Language:English
Published: 2015
Subjects:
Online Access:https://hdl.handle.net/10356/106127
http://hdl.handle.net/10220/24984
Tags: Add Tag
No Tags, Be the first to tag this record!
Institution: Nanyang Technological University
Language: English
id sg-ntu-dr.10356-106127
record_format dspace
spelling sg-ntu-dr.10356-1061272023-02-28T17:06:27Z Genome-wide analysis in Plasmodium falciparum reveals early and late phases of RNA polymerase II occupancy during the infectious cycle Rai, Ragini Zhu, Lei Chen, Haifen Gupta, Archana Patkar Sze, Siu Kwan Zheng, Jie Ruedl, Christiane Bozdech, Zbynek Featherstone, Mark School of Computer Engineering School of Biological Sciences DRNTU::Science::Biological sciences Background: Over the course of its intraerythrocytic developmental cycle (IDC), the malaria parasite Plasmodium falciparum tightly orchestrates the rise and fall of transcript levels for hundreds of genes. Considerable debate has focused on the relative importance of transcriptional versus post-transcriptional processes in the regulation of transcript levels. Enzymatically active forms of RNAPII in other organisms have been associated with phosphorylation on the serines at positions 2 and 5 of the heptad repeats within the C-terminal domain (CTD) of RNAPII. We reasoned that insight into the contribution of transcriptional mechanisms to gene expression in P. falciparum could be obtained by comparing the presence of enzymatically active forms of RNAPII at multiple genes with the abundance of their associated transcripts. Results: We exploited the phosphorylation state of the CTD to detect enzymatically active forms of RNAPII at most P. falciparum genes across the IDC. We raised highly specific monoclonal antibodies against three forms of the parasite CTD, namely unphosphorylated, Ser5-P and Ser2/5-P, and used these in ChIP-on-chip type experiments to map the genome-wide occupancy of RNAPII. Our data reveal that the IDC is divided into early and late phases of RNAPII occupancy evident from simple bi-phasic RNAPII binding profiles. By comparison to mRNA abundance, we identified sub-sets of genes with high occupancy by enzymatically active forms of RNAPII and relatively low transcript levels and vice versa. We further show that the presence of active and repressive histone modifications correlates with RNAPII occupancy over the IDC. Conclusions: The simple early/late occupancy by RNAPII cannot account for the complex dynamics of mRNA accumulation over the IDC, suggesting a major role for mechanisms acting downstream of RNAPII occupancy in the control of gene expression in this parasite. NMRC (Natl Medical Research Council, S’pore) Published version 2015-01-27T09:05:14Z 2019-12-06T22:05:06Z 2015-01-27T09:05:14Z 2019-12-06T22:05:06Z 2014 2014 Journal Article Rai, R., Zhu, L., Chen, H., Gupta, A. P., Sze, S. K., Zheng, J., et al. (2014). Genome-wide analysis in Plasmodium falciparum reveals early and late phases of RNA polymerase II occupancy during the infectious cycle. BMC Genomics, 15(1), 959-. 1471-2164 https://hdl.handle.net/10356/106127 http://hdl.handle.net/10220/24984 10.1186/1471-2164-15-959 25373614 en BMC Genomics © 2014 Rai et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. 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. 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
Rai, Ragini
Zhu, Lei
Chen, Haifen
Gupta, Archana Patkar
Sze, Siu Kwan
Zheng, Jie
Ruedl, Christiane
Bozdech, Zbynek
Featherstone, Mark
Genome-wide analysis in Plasmodium falciparum reveals early and late phases of RNA polymerase II occupancy during the infectious cycle
description Background: Over the course of its intraerythrocytic developmental cycle (IDC), the malaria parasite Plasmodium falciparum tightly orchestrates the rise and fall of transcript levels for hundreds of genes. Considerable debate has focused on the relative importance of transcriptional versus post-transcriptional processes in the regulation of transcript levels. Enzymatically active forms of RNAPII in other organisms have been associated with phosphorylation on the serines at positions 2 and 5 of the heptad repeats within the C-terminal domain (CTD) of RNAPII. We reasoned that insight into the contribution of transcriptional mechanisms to gene expression in P. falciparum could be obtained by comparing the presence of enzymatically active forms of RNAPII at multiple genes with the abundance of their associated transcripts. Results: We exploited the phosphorylation state of the CTD to detect enzymatically active forms of RNAPII at most P. falciparum genes across the IDC. We raised highly specific monoclonal antibodies against three forms of the parasite CTD, namely unphosphorylated, Ser5-P and Ser2/5-P, and used these in ChIP-on-chip type experiments to map the genome-wide occupancy of RNAPII. Our data reveal that the IDC is divided into early and late phases of RNAPII occupancy evident from simple bi-phasic RNAPII binding profiles. By comparison to mRNA abundance, we identified sub-sets of genes with high occupancy by enzymatically active forms of RNAPII and relatively low transcript levels and vice versa. We further show that the presence of active and repressive histone modifications correlates with RNAPII occupancy over the IDC. Conclusions: The simple early/late occupancy by RNAPII cannot account for the complex dynamics of mRNA accumulation over the IDC, suggesting a major role for mechanisms acting downstream of RNAPII occupancy in the control of gene expression in this parasite.
author2 School of Computer Engineering
author_facet School of Computer Engineering
Rai, Ragini
Zhu, Lei
Chen, Haifen
Gupta, Archana Patkar
Sze, Siu Kwan
Zheng, Jie
Ruedl, Christiane
Bozdech, Zbynek
Featherstone, Mark
format Article
author Rai, Ragini
Zhu, Lei
Chen, Haifen
Gupta, Archana Patkar
Sze, Siu Kwan
Zheng, Jie
Ruedl, Christiane
Bozdech, Zbynek
Featherstone, Mark
author_sort Rai, Ragini
title Genome-wide analysis in Plasmodium falciparum reveals early and late phases of RNA polymerase II occupancy during the infectious cycle
title_short Genome-wide analysis in Plasmodium falciparum reveals early and late phases of RNA polymerase II occupancy during the infectious cycle
title_full Genome-wide analysis in Plasmodium falciparum reveals early and late phases of RNA polymerase II occupancy during the infectious cycle
title_fullStr Genome-wide analysis in Plasmodium falciparum reveals early and late phases of RNA polymerase II occupancy during the infectious cycle
title_full_unstemmed Genome-wide analysis in Plasmodium falciparum reveals early and late phases of RNA polymerase II occupancy during the infectious cycle
title_sort genome-wide analysis in plasmodium falciparum reveals early and late phases of rna polymerase ii occupancy during the infectious cycle
publishDate 2015
url https://hdl.handle.net/10356/106127
http://hdl.handle.net/10220/24984
_version_ 1759853116023373824