Malaria parasite transcription repressor AP2-O3 regulates sex-specific identity of gene expression in female gametocytes
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ABSTRACT:
ORGANISM(S): Plasmodium yoelii yoelii
PROVIDER: GSE157457 | GEO | 2021/01/26
REPOSITORIES: GEO
Similar Datasets
Project description:Male and female gametocytes are sexual precursor cells essential for mosquito transmission of malaria parasite. Differentiation of gametocytes into fertile gametes (known as gametogenesis) relies on the gender-specific transcription program. How the parasites establish distinct repertoires of transcription in the male and female gametocytes remains largely unknown. Here, we report that an Apetala2 family transcription factor AP2-O3 operates as a transcription repressor in the female gametocytes. AP2-O3 is specifically expressed in the female gametocytes. AP2-O3-deficient parasites produce apparently normal female gametocytes. Nevertheless, these gametocytes fail to differentiate into fully fertile female gametes, leading to developmental arrest in fertilization and early development post-fertilization. AP2-O3 disruption causes massive upregulation of transcriptionally dormant male genes and simultaneously downregulation of highly transcribed female genes in the female gametocytes. AP2-O3 targets a substantial proportion of the male genes by recognizing an 8-base DNA motif. In addition, the maternal AP2-O3 is removed after fertilization, which is required for the zygote to ookinete development. Therefore, the global transcriptional repression of the male genes in the female gametocytes is required for safeguarding female-specific transcriptome and essential for the mosquito transmission of Plasmodium.
| S-EPMC8097350 | biostudies-literature
Project description:Male and female gametocytes are sexual precursor cells essential for transmission of malaria parasite in the mosquitoes. Differentiation of gametocytes to fertile gametes (gametogenesis) relies on the gender-specific transcriptome. However, how the parasites establish distinct repertoire of gene transcription in the male and female gametocytes remains largely unknown. Here, we report that an Apetala2 (AP2) family transcription factor (TF) AP2-O3 operates as a transcription repressor regulating female gametocyte transcriptome. AP2-O3 is specifically localized in the nucleus of the female gametocytes. AP2-O3-deficient parasites produce apparently normal female gametocytes, which fail to differentiate to fully fertile female gametes, leading to developmental arrest in fertilization and early development post-fertilization. AP2-O3 disruption causes massive up-regulation of transcriptionally dormant male genes and simultaneously down-regulation of highly transcribed female genes in female gametocytes. ChIP-seq and EMSA analysis establish AP2-O3 as a transcription repressor that targets a significant proportion of the upregulated male genes by recognizing an eight-base DNA motif in the promoters. In addition, the maternal AP2-O3 is removed after fertilization, which is required for the zygote to ookinete development. These results demonstrate that global transcriptional repression of male genes in the female gametocytes is required for safeguarding female-specific transcriptome and essential for the mosquito transmission of Plasmodium.
2021-01-26 | GSE157454 | GEO
Project description:Male and female gametocytes are sexual precursor cells essential for transmission of malaria parasite in the mosquitoes. Differentiation of gametocytes to fertile gametes (gametogenesis) relies on the gender-specific transcriptome. However, how the parasites establish distinct repertoire of gene transcription in the male and female gametocytes remains largely unknown. Here, we report that an Apetala2 (AP2) family transcription factor (TF) AP2-O3 operates as a transcription repressor regulating female gametocyte transcriptome. AP2-O3 is specifically localized in the nucleus of the female gametocytes. AP2-O3-deficient parasites produce apparently normal female gametocytes, which fail to differentiate to fully fertile female gametes, leading to developmental arrest in fertilization and early development post-fertilization. AP2-O3 disruption causes massive up-regulation of transcriptionally dormant male genes and simultaneously down-regulation of highly transcribed female genes in female gametocytes. ChIP-seq and EMSA analysis establish AP2-O3 as a transcription repressor that targets a significant proportion of the upregulated male genes by recognizing an eight-base DNA motif in the promoters. In addition, the maternal AP2-O3 is removed after fertilization, which is required for the zygote to ookinete development. These results demonstrate that global transcriptional repression of male genes in the female gametocytes is required for safeguarding female-specific transcriptome and essential for the mosquito transmission of Plasmodium.
2021-01-26 | GSE157456 | GEO
Project description:Malaria parasite transcription repressor AP2-O3 regulates sex-specific identity of gene expression in female gametocytes
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Project description:Plasmodium transcription repressor AP2-O3 regulates sex-specific identity of gene expression in female gametocytes [RNA-seq]
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Project description:Plasmodium transcription repressor AP2-O3 regulates sex-specific identity of gene expression in female gametocytes [ChIP-seq]
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Project description:The gametocytes of the malaria parasites are obligate for perpetuating the parasite's life cycle through mosquitoes, but the sex-specific biology of gametocytes is poorly understood. We generated a transgenic line in the human malaria parasite Plasmodium falciparum, which allowed us to accurately separate male and female gametocytes by flow cytometry. In-depth analysis of the proteomes by liquid chromatography-tandem mass spectrometry identified 1244 and 1387 proteins in mature male and female gametocytes, respectively. GFP-tagging of nine selected proteins confirmed their sex-partitions to be agreeable with the results from the proteomic analysis. The sex-specific proteomes showed significant differences that are consistent with the divergent functions of the two sexes. Although the male-specific proteome (119 proteins) is enriched in proteins associated with the flagella and genome replication, the female-specific proteome (262 proteins) is more abundant in proteins involved in metabolism, translation and organellar functions. Compared with the Plasmodium berghei sex-specific proteomes, this study revealed both extensive conservation and considerable divergence between these two species, which reflect the disparities between the two species in proteins involved in cytoskeleton, lipid metabolism and protein degradation. Comparison with three sex-specific proteomes allowed us to obtain high-confidence lists of 73 and 89 core male- and female-specific/biased proteins conserved in Plasmodium The identification of sex-specific/biased proteomes in Plasmodium lays a solid foundation for understanding the molecular mechanisms underlying the unique sex-specific biology in this early-branching eukaryote.
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Project description:AP2-FG is a female-specific transcription factor (TF) that plays an essential role in female gametocyte development. AP2-FG activates hundreds of genes by binding to a female-specific ten-base cis-acting element. Here, we report that in the rodent malaria parasite Plasmodium berghei, another female-specific TF designated as a partner of AP2-FG (PFG), controls gene expression in female gametocytes cooperatively with AP2-FG. Transcriptional mechanisms were analyzed in Plasmodium berghei female gametocytes.
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Project description:In the human host, Plasmodium falciparum parasites propagate asexually in erythrocytes causing the symptoms of malaria. However, in every asexual cycle, a small proportion of the parasites commits to sexual differentiation, which is critical for transmission. During a period of about 10 days, the sexually committed parasites either develop into male or female gametocytes. In this study, gametocytes carrying an endogenously GFP tagged version of the female specifically expressed ABCG2 gene were FACS sorted to separate male (GFP low) and female (GFP high) gametocyte populations at different days of development. RNA was subsequently extracted from these populations as well as from asexual parasites as controls and subjected to directional RNAseq. These data reveal the transcriptional differences between asexual parasite stages and developing gametocytes, but also between male and female gametocytes as well as for each sex during the course of differentiation. In particular, male gametocytes undergo distinct transcriptional transitions when comparing the transcriptome between day 4, 6 and 10 of gametocytogenesis. In contrast, female gametocyte transcriptomes are more static during the course of gametocytogenesis and only show minimal variation. This is the first study to longitudinally monitor gene expression in developing male and female gametocytes
2021-07-31 | GSE180985 | GEO
Project description:Plasmodium falciparum parasites alternate between two different obligate hosts during their life cycle: humans and Anopheles mosquitoes. During the blood stage in the human host they proliferate asexually inside erythrocytes. A small proportion of parasites develops into male and female gametocytes, which enter the sexual part of the life cycle once taken up by a mosquito. The production of male and female gametocytes is therefore critical for malaria transmission. It has been shown that epigenetic processes play a role in this differentiation processes, however, the exact mechanisms remain unknown. To gain insight into these processes, we separated male and female gametocytes, based on the female specific expression of an endogenously GFP-tagged ABCG2 gene, using flow cytometry (male parasites as GFP low, female parasites as GFP high population). We subsequently performed ChIP-Seq for several histone variants and modifications (H2A.Z, H2A.Zac, H2B.Z, H3K4me3, H3R17me2, H3K27ac, H3K9me3) on day 6 of gametocytogenesis. Our study reveals a global remodelling of the chromatin landscape in gametocytes compared to asexual parasites, as well as sex specific differences.
2022-05-07 | GSE202214 | GEO