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The effect of CDK6 expression on DNA methylation, DNMT3B regulation, and the transcriptome

ABSTRACT: The effect of CDK6 expression on DNA methylation, DNMT3B regulation, and the transcriptome

PROVIDER: PRJNA606353 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR11075900.fastq.gz	Fastqsanger.gz
	SRR11075901.fastq.gz	Fastqsanger.gz
	SRR11075902.fastq.gz	Fastqsanger.gz
	SRR11075903.fastq.gz	Fastqsanger.gz
	SRR11075904.fastq.gz	Fastqsanger.gz

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The effect of CDK6 expression on DNA methylation and DNMT3B regulation

Project description:The effect of CDK6 expression on DNA methylation and DNMT3B regulation

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The effect of CDK6 expression on DNA methylation and DNMT3B regulation

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The Effect of CDK6 Expression on DNA Methylation and DNMT3B Regulation.

Project description:CDK6 is frequently overexpressed in various cancer types and functions as a positive regulator of the cell cycle and as a coregulator of gene transcription. We provide evidence that CDK6 is involved in the process of DNA methylation, at least in ALL. We observe a positive correlation of CDK6 and DNMT expression in a large number of ALL samples. ChIP-seq analysis reveals CDK6 binding to genomic regions associated with DNA methyltransferases (DNMTs). ATAC-seq shows a strong reduction in chromatin accessibility for DNMT3B in CDK6-deficient BCR-ABL + Cdk6-/- cells, accompanied by lower levels of DNMT3B mRNA and less chromatin-bound DNMT3B, as shown by RNA-seq and chromatome analysis. Motif analysis suggests that ETS family members interact with CDK6 to regulate DNMT3B. Reduced representation bisulfite sequencing analysis uncovers reversible and cell line-specific changes in DNA methylation patterns upon CDK6 loss. The results reveal a function of CDK6 as a regulator of DNA methylation in transformed cells.

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Increased DNA Methylation of Dnmt3b-Targets Impairs Leukemogenesis (RRBS)

Project description:The de novo DNA methyltransferases Dnmt3a and Dnmt3b are of crucial importance in hematopoietic stem cells, and Dnmt3b has recently been shown to play a role in genic methylation. Forced Dnmt3b expression induced widespread DNA hypermethylation in myc-bcl2 induced leukemias, especially at promoters and gene bodies of stem cell-related genes. MLL-AF9 induced leukemogenesis showed much less pronounced DNA hypermethylation upon Dnmt3b expression. Nonetheless, leukemogenesis was delayed in both models with a shared core set of DNA hypermethylated regions and suppression of stem cell-related genes. Our findings indicate a critical role for Dnmt3b-mediated DNA methylation in leukemia development and maintenance of LSC function. To investigate how Dnmt3b-mediated DNA methylation affects leukemogenesis, we analyzed leukemia development under conditions of high and physiological methylation levels in a tetracycline-inducible knockin mouse model. High expression of Dnmt3b slowed leukemia development in serial transplantations and impaired leukemia stem cell (LSC) function.

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The effect of CDK6 expression on DNA methylation, DNMT3B regulation, and the transcriptome

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

2020-11-24 | GSE145220 | GEO