The PfAP2-G2 transcription factor is a critical regulator of gametocyte maturation

Suprita Singh; Joana M. Santos; Lindsey M. Orchard; Naomi Yamada; Riëtte van Biljon; Heather J. Painter; Shaun Mahony; Manuel Llinás

doi:10.1111/mmi.14676

The PfAP2-G2 transcription factor is a critical regulator of gametocyte maturation

Suprita Singh, Joana M. Santos, Lindsey M. Orchard, Naomi Yamada, Riëtte van Biljon, Heather J. Painter, Shaun Mahony, Manuel Llinás

Research output: Contribution to journal › Article › peer-review

21 Scopus citations

Abstract

Differentiation from asexual blood stages to mature sexual gametocytes is required for the transmission of malaria parasites. Here, we report that the ApiAP2 transcription factor, PfAP2-G2 (PF3D7_1408200) plays a critical role in the maturation of Plasmodium falciparum gametocytes. PfAP2-G2 binds to the promoters of a wide array of genes that are expressed at many stages of the parasite life cycle. Interestingly, we also find binding of PfAP2-G2 within the gene body of almost 3,000 genes, which strongly correlates with the location of H3K36me3 and several other histone modifications as well as Heterochromatin Protein 1 (HP1), suggesting that occupancy of PfAP2-G2 in gene bodies may serve as an alternative regulatory mechanism. Disruption of pfap2-g2 does not impact asexual development, but the majority of sexual parasites are unable to mature beyond stage III gametocytes. The absence of pfap2-g2 leads to overexpression of 28% of the genes bound by PfAP2-G2 and none of the PfAP2-G2 bound genes are downregulated, suggesting that it is a repressor. We also find that PfAP2-G2 interacts with chromatin remodeling proteins, a microrchidia (MORC) protein, and another ApiAP2 protein (PF3D7_1139300). Overall our data demonstrate that PfAP2-G2 establishes an essential gametocyte maturation program in association with other chromatin-related proteins.

Original language	English (US)
Pages (from-to)	1005-1024
Number of pages	20
Journal	Molecular Microbiology
Volume	115
Issue number	5
DOIs	https://doi.org/10.1111/mmi.14676
State	Published - May 2021

All Science Journal Classification (ASJC) codes

Microbiology
Molecular Biology

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10.1111/mmi.14676

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@article{35472b8333d946939dd8950c3a691398,

title = "The PfAP2-G2 transcription factor is a critical regulator of gametocyte maturation",

abstract = "Differentiation from asexual blood stages to mature sexual gametocytes is required for the transmission of malaria parasites. Here, we report that the ApiAP2 transcription factor, PfAP2-G2 (PF3D7_1408200) plays a critical role in the maturation of Plasmodium falciparum gametocytes. PfAP2-G2 binds to the promoters of a wide array of genes that are expressed at many stages of the parasite life cycle. Interestingly, we also find binding of PfAP2-G2 within the gene body of almost 3,000 genes, which strongly correlates with the location of H3K36me3 and several other histone modifications as well as Heterochromatin Protein 1 (HP1), suggesting that occupancy of PfAP2-G2 in gene bodies may serve as an alternative regulatory mechanism. Disruption of pfap2-g2 does not impact asexual development, but the majority of sexual parasites are unable to mature beyond stage III gametocytes. The absence of pfap2-g2 leads to overexpression of 28% of the genes bound by PfAP2-G2 and none of the PfAP2-G2 bound genes are downregulated, suggesting that it is a repressor. We also find that PfAP2-G2 interacts with chromatin remodeling proteins, a microrchidia (MORC) protein, and another ApiAP2 protein (PF3D7_1139300). Overall our data demonstrate that PfAP2-G2 establishes an essential gametocyte maturation program in association with other chromatin-related proteins.",

author = "Suprita Singh and Santos, {Joana M.} and Orchard, {Lindsey M.} and Naomi Yamada and {van Biljon}, Ri{\"e}tte and Painter, {Heather J.} and Shaun Mahony and Manuel Llin{\'a}s",

note = "Funding Information: This project was largely funded by NIH/NIAID 1R01 AI125565 (ML). NY and SM were supported by R01 GM121613 (SM) and JMS was supported by a Swiss National Fund GEP3-13613 and EMBO Long-Term Fellowship 633-2011. We thank Kelly Rios for assistance with proteomic data analysis and Scott Lindner for critical feedback. Publisher Copyright: {\textcopyright} 2021 John Wiley & Sons Ltd",

year = "2021",

month = may,

doi = "10.1111/mmi.14676",

language = "English (US)",

volume = "115",

pages = "1005--1024",

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T1 - The PfAP2-G2 transcription factor is a critical regulator of gametocyte maturation

AU - Singh, Suprita

AU - Santos, Joana M.

AU - Orchard, Lindsey M.

AU - Yamada, Naomi

AU - van Biljon, Riëtte

AU - Painter, Heather J.

AU - Mahony, Shaun

AU - Llinás, Manuel

N1 - Funding Information: This project was largely funded by NIH/NIAID 1R01 AI125565 (ML). NY and SM were supported by R01 GM121613 (SM) and JMS was supported by a Swiss National Fund GEP3-13613 and EMBO Long-Term Fellowship 633-2011. We thank Kelly Rios for assistance with proteomic data analysis and Scott Lindner for critical feedback. Publisher Copyright: © 2021 John Wiley & Sons Ltd

PY - 2021/5

Y1 - 2021/5

N2 - Differentiation from asexual blood stages to mature sexual gametocytes is required for the transmission of malaria parasites. Here, we report that the ApiAP2 transcription factor, PfAP2-G2 (PF3D7_1408200) plays a critical role in the maturation of Plasmodium falciparum gametocytes. PfAP2-G2 binds to the promoters of a wide array of genes that are expressed at many stages of the parasite life cycle. Interestingly, we also find binding of PfAP2-G2 within the gene body of almost 3,000 genes, which strongly correlates with the location of H3K36me3 and several other histone modifications as well as Heterochromatin Protein 1 (HP1), suggesting that occupancy of PfAP2-G2 in gene bodies may serve as an alternative regulatory mechanism. Disruption of pfap2-g2 does not impact asexual development, but the majority of sexual parasites are unable to mature beyond stage III gametocytes. The absence of pfap2-g2 leads to overexpression of 28% of the genes bound by PfAP2-G2 and none of the PfAP2-G2 bound genes are downregulated, suggesting that it is a repressor. We also find that PfAP2-G2 interacts with chromatin remodeling proteins, a microrchidia (MORC) protein, and another ApiAP2 protein (PF3D7_1139300). Overall our data demonstrate that PfAP2-G2 establishes an essential gametocyte maturation program in association with other chromatin-related proteins.

AB - Differentiation from asexual blood stages to mature sexual gametocytes is required for the transmission of malaria parasites. Here, we report that the ApiAP2 transcription factor, PfAP2-G2 (PF3D7_1408200) plays a critical role in the maturation of Plasmodium falciparum gametocytes. PfAP2-G2 binds to the promoters of a wide array of genes that are expressed at many stages of the parasite life cycle. Interestingly, we also find binding of PfAP2-G2 within the gene body of almost 3,000 genes, which strongly correlates with the location of H3K36me3 and several other histone modifications as well as Heterochromatin Protein 1 (HP1), suggesting that occupancy of PfAP2-G2 in gene bodies may serve as an alternative regulatory mechanism. Disruption of pfap2-g2 does not impact asexual development, but the majority of sexual parasites are unable to mature beyond stage III gametocytes. The absence of pfap2-g2 leads to overexpression of 28% of the genes bound by PfAP2-G2 and none of the PfAP2-G2 bound genes are downregulated, suggesting that it is a repressor. We also find that PfAP2-G2 interacts with chromatin remodeling proteins, a microrchidia (MORC) protein, and another ApiAP2 protein (PF3D7_1139300). Overall our data demonstrate that PfAP2-G2 establishes an essential gametocyte maturation program in association with other chromatin-related proteins.

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EP - 1024

JO - Molecular Microbiology

JF - Molecular Microbiology

IS - 5

ER -

The PfAP2-G2 transcription factor is a critical regulator of gametocyte maturation

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