Histone Lysine Crotonylation Regulates Long-Term Memory Storage
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE281007 | GEO | 2024/11/13
REPOSITORIES: GEO
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Project description:Histone Lysine Crotonylation Regulates Long-Term Memory Storage
| PRJNA1181824 | ENA
Project description:Lysine crotonylation on histones is a recently identified post-translational modification that has been demonstrated to associate with active promoters and to directly stimulate transcription.Given that crotonyl-CoA is essential for the acyl transfer reaction and it is a metabolic intermediate widely localized within the cell, we postulate that lysine crotonylation on non-histone proteins could also widely exist. Using specific antibody to enrich crotonylated lysine(Kcr) peptides followed by high-resolution mass spectrometry analysis reveals that crotonylated proteins and lysine residues. Bioinformatic analysis reveals that crotonylated proteins are particularly enriched in the nuclei, that lysine crotonylation alters level of the modified proteins in the chromatin and that cotonylation of a subset of proteins influences DNA replication and cell cycle. Taken together, our data indicate that lysine crotonylation could be induced in a large number of proteins other than histones and this type of acyl modification could play an important role regulating multiple cellular processes.
2016-06-11 | MSV000079810 | MassIVE
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).
2011-10-06 | E-GEOD-32663 | biostudies-arrayexpress
Project description:Histone lysine acetylation and methylation regulate gene transcription through coordination of chromatin structure and transcriptional activity. However, our understanding of the role of histones in gene regulation is far from complete, in part due to newly discovered novel histone modifications, whose functions are yet to be uncovered1. Here we report that histone H3 lysine 27 crotonylation (H3K27cr) is selectively recognized by the YEATS domain of GAS41 in association with SIN3a-HDAC1/2 co-repressor complex for gene transcriptional repression. The GAS41 YEATS domain dimer binds proto-oncogenic transcription factor c-Myc, which recruits GAS41/SIN3a-HDAC1/2 complex to target gene loci in chromatin such as cell cycle inhibitor p21. Transcriptional de-repression of p21, directed by tumor suppressor p53 upon doxorubicin stimulation, entails dissociation of c-Myc/GAS41/SIN3a-HDAC1/2 complex from chromatin, reduced H3K27 crotonylation, and consequentially increased H3K27 acetylation at p21 locus. GAS41 knockout or H3K27cr binding depletion with CRISPR/Cas9 results in p21 activation, cell cycle arrest and tumor growth inhibition in mice. Our study explains mechanistically causal effect of GAS41 and c-Myc gene amplification on down-regulation of p21 in human colorectal cancer, and suggests GAS41 as an anti-cancer target. We propose that H3K27 crotonylation represents a previously unrecognized, distinct chromatin state for gene transcriptional repression in contrast to H3K27 trimethylation for long-term transcriptional silencing and H3K27 acetylation for transcriptional activation.
2023-10-03 | GSE128590 | GEO
Project description:Histone lysine crotonylation (Kcr) is a newly discovered post-translational modification (PTM) existing in mammalian. To assess relevance in histone Kcr and genome, we performed on genomic localization analysis of histone Kcr by ChIP-seq analysis.
2018-06-01 | GSE108542 | GEO
Project description:Lysine Catabolism Reprograms Tumour Immunity through Histone Crotonylation.
| PRJNA860225 | ENA
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.
2024-06-18 | GSE241193 | GEO
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.
2024-06-18 | GSE241194 | GEO
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.
2022-10-03 | GSE214619 | GEO