Plasmodium histone H3 clipping
Ontology highlight
ABSTRACT:
PROVIDER: PRJEB18114 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| ERR1742700.fastq.gz | Fastqsanger.gz | |||
| ERR1742880.fastq.gz | Fastqsanger.gz | |||
| ERR1743410.fastq.gz | Fastqsanger.gz | |||
| ERR1742701.fastq.gz | Fastqsanger.gz | |||
| ERR1743411.fastq.gz | Fastqsanger.gz |
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Project description:The proteolytic cleavage of histone tails, also termed histone clipping, has been described as a mechanism for permanent removal of post-translational modifications (PTMs) from histone proteins. Such activity has been ascribed to ensure regulatory function in key cellular processes such as differentiation, senescence and transcriptional control for which different histone-specific proteases has been described. However, all these studies were exclusively performed using cell lines cultured in vitro and no clear evidences that histone clipping is regulated in vivo has been reported. Here we show that histone H3 N-terminal tails undergo extensive cleavage in the differentiated cells of the villi fraction of the mouse intestinal epithelium. Combining biochemical methods, 3D organoids cultures and in vivo approaches, we demonstrate that intestinal H3 clipping is the result of multiple proteolytic activities. We identified Trypsins and Cathepsin L as specific H3 tail proteases active in small intestinal differentiated cells and showed that their proteolytic activity is differentially affected by the PTM pattern of histone H3 tails. Together, our findings provide in vivo evidences of H3 tail proteolysis in mammalian tissues directly linking H3 clipping to cell differentiation.
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Project description:There is growing evidence that proteolytic cleavage of histone N-terminal tails, known as histone clipping, influences nucleosome dynamics and functional properties. Using middle-down MS analysis we characterized intact and proteolytically processed histone H3 proteoforms isolated from human hepatocarcinoma cell line HepG2/C3A grown in 3D culture.
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Project description:The proteolytic cleavage of histone tails, also termed histone clipping, has been described as a mechanism for permanent removal of post-translational modifications (PTMs) from histone proteins. Such activity has been ascribed to ensure regulatory function in key cellular processes such as differentiation, senescence and transcriptional control for which different histone-specific proteases has been described. However, all these studies were exclusively performed using cell lines cultured in vitro and no clear evidences that histone clipping is regulated in vivo has been reported. Here we show that histone H3 N-terminal tails undergo extensive cleavage in the differentiated cells of the villi fraction of the mouse intestinal epithelium and we investigate histone PTM changes in full-length compared with clipped histone H3.
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Project description:Lifecycle progression of the malaria parasite Plasmodium falciparum requires a finely tuned regulation of gene expression including histone methylation. The histone methyltransferase PfSET10 was previously identified as a histone H3 lysine K4 methyltransferase involved in var gene regulation, making it a prominent antimalarial target. We here investigated the role of PfSET10 in the P. falciparum blood stages in more detail, using tagged PfSET10-knockout (KO) and -knockdown (KD) lines. We demonstrated a nuclear localization of PfSET10 in the P. falciparum blood stages with peak protein levels in schizonts. PfSET10 deficiency resulted in reduced intraerythrocytic growth, but had no effect on gametocyte formation. When the PfSET10-KO line was screened for histone methylation variations, lack of PfSET10 rendered the parasites unable to mark H3K18me1, while no significant changes in the H3K4 methylation status were observed. Comparative transcriptomic profiling of PfSET10-KO schizonts demonstrated the up-regulation of transcripts particularly encoding proteins of erythrocyte invasion and multi gene family proteins, suggesting a suppressive function of the histone methylation mark. TurboID coupled with mass spectrometry further revealed an extensive nuclear PfSET10 interaction network with roles in transcriptional regulation, DNA replication and repair, chromatin remodeling and mRNA processing. Main interactors of PfSET10 included ApiAP2 transcription factors, epigenetic regulators, mediators of RNA polymerase II and DNA replication licensing factors. The combined data pinpoint PfSET10 as a histone H3 lysine K18 methyltransferase regulating DNA and RNA metabolic processes important for intraerythrocytic development of P. falciparum.
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