The Effect of CDK6 Expression on DNA Methylation and DNMT3B Regulation

被引：7

作者：

Heller, Gerwin ^{[1
,2
,3
]}

Nebenfuehr, Sofie ^{[3
]}

Bellutti, Florian ^{[3
]}

Uenal, Huriye ^{[3
]}

Zojer, Markus ^{[3
]}

Scheiblecker, Lisa ^{[3
]}

Sexl, Veronika ^{[3
]}

Kollmann, Karoline ^{[3
]}

机构：

[1] Med Univ Vienna, Div Oncol, Dept Med 1, A-1090 Vienna, Austria

[2] Comprehens Canc Ctr, Vienna, Austria

[3] Univ Vet Med Vienna, Inst Pharmacol & Toxicol, Dept Biomed Sci, Vet Pl 1, A-1210 Vienna, Austria

来源：

ISCIENCE | 2020年 / 23卷 / 10期

基金：

欧洲研究理事会; 奥地利科学基金会;

关键词：

CELL-CYCLE; CANCER; HETEROGENEITY; CHROMATIN; CTCF; HYPERMETHYLATION; OVEREXPRESSION; MUTATIONS; PROGNOSIS; EVOLUTION;

D O I：

10.1016/j.isci.2020.101602

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：26

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