Dissecting the role of PfAP2-G in malaria gametocytogenesis

Gabrielle A. Josling; Timothy J. Russell; Jarrett Venezia; Lindsey Orchard; Riëtte van Biljon; Heather J. Painter; Manuel Llinás

doi:10.1038/s41467-020-15026-0

Dissecting the role of PfAP2-G in malaria gametocytogenesis

Gabrielle A. Josling, Timothy J. Russell, Jarrett Venezia, Lindsey Orchard, Riëtte van Biljon, Heather J. Painter, Manuel Llinás

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

62 Scopus citations

Abstract

In the malaria parasite Plasmodium falciparum, the switch from asexual multiplication to sexual differentiation into gametocytes is essential for transmission to mosquitos. The transcription factor PfAP2-G is a key determinant of sexual commitment that orchestrates this crucial cell fate decision. Here we identify the direct targets of PfAP2-G and demonstrate that it dynamically binds hundreds of sites across the genome. We find that PfAP2-G is a transcriptional activator of early gametocyte genes, and identify differences in PfAP2-G occupancy between gametocytes derived via next-cycle and same-cycle conversion. Our data implicate PfAP2-G not only as a transcriptional activator of gametocyte genes, but also as a potential regulator of genes important for red blood cell invasion. We also find that regulation by PfAP2-G requires interaction with a second transcription factor, PfAP2-I. These results clarify the functional role of PfAP2-G during sexual commitment and early gametocytogenesis.

Original language	English (US)
Article number	1503
Journal	Nature communications
Volume	11
Issue number	1
DOIs	https://doi.org/10.1038/s41467-020-15026-0
State	Published - Dec 1 2020

All Science Journal Classification (ASJC) codes

Chemistry(all)
Biochemistry, Genetics and Molecular Biology(all)
Physics and Astronomy(all)

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1038/s41467-020-15026-0

Cite this

@article{2a9c0fe04e9848309570fcbd07c29fd4,

title = "Dissecting the role of PfAP2-G in malaria gametocytogenesis",

abstract = "In the malaria parasite Plasmodium falciparum, the switch from asexual multiplication to sexual differentiation into gametocytes is essential for transmission to mosquitos. The transcription factor PfAP2-G is a key determinant of sexual commitment that orchestrates this crucial cell fate decision. Here we identify the direct targets of PfAP2-G and demonstrate that it dynamically binds hundreds of sites across the genome. We find that PfAP2-G is a transcriptional activator of early gametocyte genes, and identify differences in PfAP2-G occupancy between gametocytes derived via next-cycle and same-cycle conversion. Our data implicate PfAP2-G not only as a transcriptional activator of gametocyte genes, but also as a potential regulator of genes important for red blood cell invasion. We also find that regulation by PfAP2-G requires interaction with a second transcription factor, PfAP2-I. These results clarify the functional role of PfAP2-G during sexual commitment and early gametocytogenesis.",

author = "Josling, {Gabrielle A.} and Russell, {Timothy J.} and Jarrett Venezia and Lindsey Orchard and {van Biljon}, Ri{\"e}tte and Painter, {Heather J.} and Manuel Llin{\'a}s",

note = "Funding Information: This work was funded through NIH grant R01 AI125565 and generous support from The Pennsylvania State University. G.A.J. is a recipient of the Sir Keith Murdoch Fellowship from the American Australian Association and a Postdoctoral Research Grant from the American Heart Association (16POST26420067). Publisher Copyright: {\textcopyright} 2020, The Author(s).",

year = "2020",

month = dec,

day = "1",

doi = "10.1038/s41467-020-15026-0",

language = "English (US)",

volume = "11",

journal = "Nature communications",

issn = "2041-1723",

publisher = "Nature Publishing Group",

number = "1",

}

TY - JOUR

T1 - Dissecting the role of PfAP2-G in malaria gametocytogenesis

AU - Josling, Gabrielle A.

AU - Russell, Timothy J.

AU - Venezia, Jarrett

AU - Orchard, Lindsey

AU - van Biljon, Riëtte

AU - Painter, Heather J.

AU - Llinás, Manuel

N1 - Funding Information: This work was funded through NIH grant R01 AI125565 and generous support from The Pennsylvania State University. G.A.J. is a recipient of the Sir Keith Murdoch Fellowship from the American Australian Association and a Postdoctoral Research Grant from the American Heart Association (16POST26420067). Publisher Copyright: © 2020, The Author(s).

PY - 2020/12/1

Y1 - 2020/12/1

N2 - In the malaria parasite Plasmodium falciparum, the switch from asexual multiplication to sexual differentiation into gametocytes is essential for transmission to mosquitos. The transcription factor PfAP2-G is a key determinant of sexual commitment that orchestrates this crucial cell fate decision. Here we identify the direct targets of PfAP2-G and demonstrate that it dynamically binds hundreds of sites across the genome. We find that PfAP2-G is a transcriptional activator of early gametocyte genes, and identify differences in PfAP2-G occupancy between gametocytes derived via next-cycle and same-cycle conversion. Our data implicate PfAP2-G not only as a transcriptional activator of gametocyte genes, but also as a potential regulator of genes important for red blood cell invasion. We also find that regulation by PfAP2-G requires interaction with a second transcription factor, PfAP2-I. These results clarify the functional role of PfAP2-G during sexual commitment and early gametocytogenesis.

AB - In the malaria parasite Plasmodium falciparum, the switch from asexual multiplication to sexual differentiation into gametocytes is essential for transmission to mosquitos. The transcription factor PfAP2-G is a key determinant of sexual commitment that orchestrates this crucial cell fate decision. Here we identify the direct targets of PfAP2-G and demonstrate that it dynamically binds hundreds of sites across the genome. We find that PfAP2-G is a transcriptional activator of early gametocyte genes, and identify differences in PfAP2-G occupancy between gametocytes derived via next-cycle and same-cycle conversion. Our data implicate PfAP2-G not only as a transcriptional activator of gametocyte genes, but also as a potential regulator of genes important for red blood cell invasion. We also find that regulation by PfAP2-G requires interaction with a second transcription factor, PfAP2-I. These results clarify the functional role of PfAP2-G during sexual commitment and early gametocytogenesis.

UR - http://www.scopus.com/inward/record.url?scp=85082092623&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85082092623&partnerID=8YFLogxK

U2 - 10.1038/s41467-020-15026-0

DO - 10.1038/s41467-020-15026-0

M3 - Article

C2 - 32198457

AN - SCOPUS:85082092623

SN - 2041-1723

VL - 11

JO - Nature communications

JF - Nature communications

IS - 1

M1 - 1503

ER -

Dissecting the role of PfAP2-G in malaria gametocytogenesis

Abstract

All Science Journal Classification (ASJC) codes

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this