The Effect of CDK6 Expression on DNA Methylation and DNMT3B Regulation

IScience
Gerwin HellerKaroline Kollmann

Abstract

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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Citations

Jul 13, 2021·Frontiers in Immunology·Klara KleinVeronika Sexl
Oct 16, 2021·Neurotoxicity Research·Licheng ZhangFengying Guo

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Datasets Mentioned

BETA
GSE113752

Methods Mentioned

BETA
methylation aberrations
ChIP-seq
RNA-seq
RRBS
PCA

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