Kaiso Regulates DNA Methylation Homeostasis

International Journal of Molecular Sciences

Kristina Gainova¹  Fedor Sharko²  Egor Prokhortchouk²  Nadezhda Zhigalova²  Darya Kaplun²  Alexey Starshin²  Alexander Mazur²  Svetlana Zhenilo²  Galina Filonova² 

[1] Centre for Strategic Planning of FMBA of Russia, 119071 Moscow, Russia;Federal State Institution «Federal Research Centre «Fundamentals of Biotechnology» of the Russian Academy of Sciences», 119071 Moscow, Russia;

关键词: DNA methylation;    Kaiso;    cancer;    de novo DNA methyltransferases;    DNMT3a/3b;   

DOI  :  10.3390/ijms22147587

来源: DOAJ

【 摘 要 】

Gain and loss of DNA methylation in cells is a dynamic process that tends to achieve an equilibrium. Many factors are involved in maintaining the balance between DNA methylation and demethylation. Previously, it was shown that methyl-DNA protein Kaiso may attract NCoR, SMRT repressive complexes affecting histone modifications. On the other hand, the deficiency of Kaiso resulted in reduced methylation of ICR in H19/Igf2 locus and Oct4 promoter in mouse embryonic fibroblasts. However, nothing is known about how Kaiso influences DNA methylation at the genome level. Here we show that deficiency of Kaiso led to whole-genome hypermethylation, using Kaiso deficient human renal cancer cell line obtained via CRISPR/CAS9 genome editing. However, Kaiso serves to protect genic regions, enhancers, and regions with a low level of histone modifications from demethylation. We detected hypomethylation of binding sites for Oct4 and Nanog in Kaiso deficient cells. Kaiso immunoprecipitated with de novo DNA methyltransferases DNMT3a/3b, but not with maintenance methyltransferase DNMT1. Thus, Kaiso may attract methyltransferases to surrounding regions and modulate genome methylation in renal cancer cells apart from being methyl DNA binding protein.

【 授权许可】

Unknown