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

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

PROVIDER: PRJNA1006716 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR25689328_1.fastq.gz	Fastqsanger.gz
	SRR25689328_2.fastq.gz	Fastqsanger.gz
	SRR25689329_1.fastq.gz	Fastqsanger.gz
	SRR25689329_2.fastq.gz	Fastqsanger.gz
	SRR25689330_1.fastq.gz	Fastqsanger.gz

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P300 Regulates Histone Crotonylation and Preimplantation Embryo Development

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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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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 report the identification of 67 previously undescribed histone modifications, increasing the current number of known histone marks by about 70%. We further investigated one of the marks, lysine crotonylation (Kcr), confirming that it represents an evolutionarily-conserved histone posttranslational modification. The unique structure and genomic localization of histone Kcr suggest that it is mechanistically and functionally different from histone lysine acetylation (Kac). Specifically, in both human somatic and mouse male germ cell genomes, histone Kcr marks either active promoters or potential enhancers. In male germinal cells immediately following meiosis, Kcr is enriched on sex chromosomes and specifically marks testis-specific genes, including a significant proportion of X-linked genes that escape sex chromosome inactivation in haploid cells. These results therefore dramatically extend the repertoire of histone PTM sites and designate Kcr as a specific mark of active sex chromosome-linked genes in postmeiotic male germ cells. 2 histone marks (pan-lysine acetylation and pan-lysine crotonylation) were studied in 1 human cell type and 2 mouse cell types using ChIP-Seq. Input was sequenced for each cell type as a control. Pan-anti_Kac and pan-anti_Kcr antibodies were custom developed with PTM BioLab, Co., Ltd (Chicago, IL).

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