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Histone crotonylation and its readers control virulence-related biology of a major human commensal and pathogen.

ABSTRACT: Histone crotonylation and its readers control virulence-related biology of a major human commensal and pathogen.

PROVIDER: PRJNA526940 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR8724890.fastq.gz	Fastqsanger.gz
	SRR8724891.fastq.gz	Fastqsanger.gz
	SRR8724884.fastq.gz	Fastqsanger.gz
	SRR8724885.fastq.gz	Fastqsanger.gz
	SRR8724886.fastq.gz	Fastqsanger.gz

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Histone crotonylation and its readers control virulence-related biology of a major human commensal and pathogen.

Project description:Histone crotonylation and its readers control virulence-related biology of a major human commensal and pathogen.

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Histone crotonylation and its readers control virulence-related biology of a major human commensal and pathogen.

Project description:PAT-seq approach was utilised to determine the gene expression of C. albicans. Biological duplicates of wild type and taf14∆∆ mutant samples were grown to log phase, with or without crotonate treatment (50 mM, 2 h).

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Histone crotonylation and its readers control virulence-related biology of a major human commensal and pathogen.

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Project description:Histone crotonylation

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In vivo commensal control of Clostridioides difficile virulence

Project description:We illustrate how metabolically distinct species of Clostridia can protect against or worsen Clostridioides difficile infection, modulating the pathogen's colonization, growth, and virulence to impact host survival. Gnotobiotic mice colonized with the amino acid fermenter Paraclostridium bifermentans survived infection while mice colonized with the butyrate-producer, Clostridium sardiniense, more rapidly succumbed. Systematic in vivo analyses revealed how each commensal altered the gut nutrient environment, modulating the pathogen's metabolism, regulatory networks, and toxin production. Oral administration of P. bifermentans rescued conventional mice from lethal C. difficile infection via mechanisms identified in specifically colonized mice. Our findings lay the foundation for mechanistically informed therapies to counter C. difficile disease using systems biologic approaches to define host-commensal-pathogen interactions in vivo.

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P300 Regulates Histone Crotonylation and Preimplantation Embryo Development (RNA-Seq)

Project description:Histone lysine crotonylation is a non-acetyl histone lysine modification that is evolutionarily conserved. It plays an important role in regulating various biological processes, including gene transcriptional regulation, spermatogenesis, and cell cycle. However, the dynamic changes and functions of histone crotonylation in preimplantation embryonic development in mammals remain unclear. In this study, we have shown that the transcription coactivator P300 functions as a writer of histone crotonylation during embryonic development. Depletion of P300 resulted in significant developmental defects and dysregulation of the transcriptome of embryos. Importantly, we demonstrated that P300 catalyzes the crotonylation of histone, directly stimulating transcription and regulating gene expression, thereby ensuring successful embryo development to the blastocyst stage. Furthermore, it is showed that the histone H3 lysine 18 crotonylation (H3K18cr) modification is predominantly located in active promoter regions. It serves as an epigenetic hallmark of key transcriptional regulators and promotes the transcription activation of genes. Together, our results propose a model wherein P300-mediated histone crotonylation plays a crucial role in regulating the fate of embryonic development.

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P300 Regulates Histone Crotonylation and Preimplantation Embryo Development (ChIP-Seq)

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Crotonylation of GAPDH regulates human embryonic stem cell endodermal lineage differentiation and metabolic switch

Project description:Post-translational modifications of proteins are crucial to the regulation of their activity and function. As a newly discovered acylation modification, crotonylation of non-histone proteins remains largely unexplored, particularly in human embryonic stem cells (hESCs). Here we report the investigation of induced crotonylation in hESCs, which resulted in hESCs of different pluripotency states differentiating into the endodermal lineage. We showed that increased protein crotonylation in hESCs was accompanied by transcriptomic shifts and decreased glycolysis. Through large-scale profiling of non-histone protein crotonylation, we showed that metabolic enzymes were major targets of inducible crotonylation in hESCs. We further discovered GAPDH as a key glycolytic enzyme regulated by crotonylation during endodermal differentiation from hESCs, where crotonylation of GAPDH decreased its enzymatic activity thereby leading to reduced glycolysis. Our study demonstrates that crotonylation of glycolytic enzymes may be crucial to metabolic switching and cell fate determination in hESCs.

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Histone crotonylation promotes endoderm differentiation. [scRNA-Seq]

Project description:In this study we report that histone crotonylation promotes human embryonic stem cell differentiation to endoderm cells. Addition of crotonate, a precursor for crotonyl-CoA and therefore histone crotonylation, dramatically enhanced endoderm cell differentiation from human embryonic stem cells, while incubation of acetate, a precursor of acetyl-CoA and therefore histone acetylation, did not change the efficiency of endoderm differentiation.

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Project description:We examined the genome-wide distribution of histone crotonylation and H3K27ac in human embryonic stem cells and induced endoderm cells, by obtaining over four billion bases of sequence from chromatin immunoprecipitated DNA. When compared to H3K27ac, histone crotonylation was more enriched in metabolic genes and in promoters at pluripotent state, while H3k27ac was enriched in the enhancers of endoderm genes. After endoderm differentiation, histone crotonylation and H3K27ac were both enriched in endoderm genes. Moreover, the enrichment of histone crotonylation was more remarkable than that of H3K27ac. Our data indicate that histone crotonylation correlates with endoderm differentiation.

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