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SRX8243388: GSM4512251: PfAP2-G5_GFP_WT_D5_rep2_INPUT_ChIP-seq; Plasmodium falciparum; ChIP-Seq
1 ILLUMINA (HiSeq X Ten) run: 18.6M spots, 5.6G bases, 1.8Gb downloads

Submitted by: NCBI (GEO)
Study: A transcriptional repressor programs gametocytogenesis in human malaria parasites (PfAP2-G5) [ChIP-Seq TF]
show Abstracthide Abstract
Gametocytogenesis, the process by which malaria parasites produce sexual forms that can infect mosquitoes, is essential for the transmission of malaria. A transcriptional switch of the pfap2-g gene triggers sexual commitment, but how the complex multi-step process is precisely programed remains largely unknown. Here, by systematic functional screening of a panel of ApiAP2 transcription factors, we identify six new apiAP2 members associated with gametocytogenesis in Plasmodium falciparum. Among these, PfAP2-G5 (PF3D7_1139300) was found to be indispensable for gametocytogenesis. This factor suppresses the transcriptional activity of the pfap2-g gene via binding to both the upstream region and exonic gene body, the latter is linked to the maintenance of local heterochromatin structure, thereby preventing initiation of sexual commitment. Removal of this repressive effect through pfap2-g5 knockout disrupts the asexual replication cycle and promotes sexual commitment accompanied by upregulation of pfap2-g expression. However, the gametocytes produced fail to mature fully. Further analyses show that PfAP2-G5 is essential for gametocyte maturation, and causes the down-regulation of pfap2-g and a set of early gametocyte genes activated by PfAP2-G prior to gametocyte development. Collectively, our findings reveal a regulation cascade of gametocyte production in malaria parasites, and provide a new target for transmission blocking interventions. Overall design: The PfAP2-G5-GFP::WT line at trophozoite (30-40hpi) and G0-G1 gametocyte (D5) stages, the PfAP2-G-GFP::WT and PfAP2-G-GFP::pfap2-g5_trun lines at trophozoite (30-40hpi) stage were harvested to perform ChIP assay using antibody against GFP or IgG. There are two biological replicates for each of the parasite lines. The input and IgG material served as the control.
Sample: PfAP2-G5_GFP_WT_D5_rep2_INPUT_ChIP-seq
SAMN14823829 • SRS6592024 • All experiments • All runs
Library:
Instrument: HiSeq X Ten
Strategy: ChIP-Seq
Source: GENOMIC
Selection: ChIP
Layout: PAIRED
Construction protocol: Synchronized PfAP2-G5-GFP::WT, PfAP2-G-GFP::WT, PfAP2-G-GFP::pfap2-g5_trun parasites at different stages were harvested and cross-linked immediately with 1% paraformaldehyde (Sigma) by rotating for 10 min at 37 ℃, then quenched with 0.125 M glycine for 5 min. The culture was resuspended with 1 x PBS and parasites were released from iRBC with 0.15% saponin for 10- 15 min on ice. The washed nuclei were isolated by incubation with 2 ml of Lysis Buffer (10 mM HEPES pH 7.9, 10 mM KCl, 0.1 mM EDTA pH8.0, 0.1mM EGTA pH8.0, 1mM DTT, 0.25% NP40, 1 x protease inhibitors cocktail) for 30 min on ice, and followed by dounce homogenization for 100 strokes. Afterwards the nuclei were resuspended in 200 μl of SDS Lysis Buffer (1% SDS, 10 mM EDTA, 50 mM Tris-HCl pH8.0) for sonication to generate 200–500 bp fragments in length. The sonicated chromatin was diluted ten-fold with dilution buffer (0.01% SDS, 1.1% Triton X-100, 1.2 mM EDTA, 16.7 mM Tris-HCl pH8.0, 150 mM NaCl, 1 x protease inhibitors cocktail) and precleared with Protein A/G magnetic beads (Pierce) for two hours. The precleared chromatin supernatant was incubated with 1 μg rabbit anti-GFP (Abcam, ab290) or rabbit IgG (Abcam) as control and Protein A/G magnetic beads at 4 ℃ overnight with a small volume of non-immunoprecipitated input material kept separately. After extensive washes, protein-DNA complexes were eluted with Elution Buffer (1% SDS, 0.1 M NaHCO3). Crosslinking was reversed by incubating overnight at 45°C and DNA was treated with RNase A at 37°C for 30 min and Proteinase K at 45°C for two hours. ChIP-DNA was extracted using MinElute PCR purification kit (Qiagen, 28006). ChIP-DNA was end-repaired (Epicentre No.ER81050), adding protruding 3' A base (NEB No.M0212L), adapter ligation(NEB No.M2200L), size selection and amplification of libraries(KAPA Biosystems, KB2500) with a PCR program: 1 min at 98 ℃, 12 cycles of 10 s at 98 ℃, 1 min at 65 ℃; finally extended 5 min at 65 ℃.
Experiment attributes:
GEO Accession: GSM4512251
Links:
Runs: 1 run, 18.6M spots, 5.6G bases, 1.8Gb
Run# of Spots# of BasesSizePublished
SRR1168255318,640,3345.6G1.8Gb2021-08-06

ID:
10745011

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