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Identification of differentially expressed tumour-related genes regulated by UHRF1 regulated DNA methylation [WGBS]

ABSTRACT: Identification of differentially expressed tumour-related genes regulated by UHRF1 regulated DNA methylation [WGBS]

PROVIDER: PRJNA1045262 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR26949323_1.fastq.gz	Fastqsanger.gz
	SRR26949323_2.fastq.gz	Fastqsanger.gz
	SRR26949324_1.fastq.gz	Fastqsanger.gz
	SRR26949324_2.fastq.gz	Fastqsanger.gz
	SRR26949325_1.fastq.gz	Fastqsanger.gz

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Identification of differentially expressed tumour-related genes regulated by UHRF1 regulated DNA methylation [WGBS]

Project description:UHRF1 is an epigenetic regulator that plays critical roles in tumours. However, the DNA methylation alteration patterns driven by UHRF1 and the related differentially expressed tumour-related genes remain unclear. In this study, a UHRF1-shRNA MCF-7 cell line was constructed, and whole-genome bisulfite sequencing (WGBS) and RNA sequencing were performed. The DNA methylation alteration landscape was elucidated, and DNA methylation-altered regions (DMRs) were found to be distributed in both gene bodies and adjacent regions. The DMRs were annotated and categorized into 488 hypermethylated/1696 hypomethylated promoters and 1149 hypermethylated/5501 hypomethylated gene bodies. Through an integrated analysis with the RNA sequencing data, 217 upregulated methylated genes and 288 downregulated methylated genes were identified, and these genes were primarily enriched in nervous system development and cancer signalling pathways.

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Identification of differentially expressed tumour-related genes regulated by UHRF1 regulated DNA methylation

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Project description:To investigate the funciton of UHRF1 in ICAM1 and pro-inflammatory genes regulaiton, we generate the UHRF1 KO cells and profiled the WGBS.

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Identification of differentially expressed tumour-related genes regulated by UHRF1 regulated DNA methylation

Project description:This SuperSeries is composed of the SubSeries listed below.

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whole-genome bisulfite sequencing (WGBS) of wild-type and Uhrf1-/- ESCs

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whole-genome bisulfite sequencing (WGBS) of wild-type and Uhrf1-/- ESCs

Project description:UHRF1 is a chromatin-binding protein essential for maintaining DNA methylation and histone modification states, yet its integrated role in vivo remains incompletely understood. To define its function, we generated conditional Uhrf1 knockout embryonic stem cells (ESCs) and embryos. Uhrf1⁻/⁻ ESCs exhibited near-complete loss of 5mC and 5hmC but maintained pluripotency, whereas Uhrf1-null embryos developed normally until E8.5 and then failed to further develop by E9.5.

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Project description:The multi-domain protein UHRF1 (ubiquitin-like, containing PHD and RING finger domains, 1) recruits DNMT1 for DNA methylation maintenance during DNA replication. Here, we show that MOF (Males absent On the First) is an acetyltransferase of UHRF1 to acetylate UHRF1 at Lys670 in the pre-RING linker region whereas HDAC1 is a deacetylase of UHRF1 at the same site. The MOF/HDAC1-mediated acetylation in UHRF1 is cell-cycle regulated and peaks at G1/S phase, in line with the function of UHRF1 in recruiting DNMT1 to maintain DNA methylation. In addition, UHRF1 acetylation significantly enhances its E3 ligase activity and elimination of UHRF1 acetylation at these sites attenuates UHRF1-mediated H3 ubiquitination, which in turn impairs the DNMT1 recruitment and DNA methylation. Taken together, these findings not only identify MOF as a new acetyltransferase for UHRF1 but also reveal a novel mechanism underlying the regulation of DNA methylation maintenance through MOF-mediated UHRF1 acetylation.

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