MBD3L2 promotes Tet2 enzymatic activity for mediating 5-methylcytosine oxidation.

Journal of Cell Science
Lina PengWenqiang Yu

Abstract

Ten-eleven translocation (Tet) proteins are key players involved in the dynamic regulation of cytosine methylation and demethylation. Inactivating mutations of Tet2 are frequently found in human malignancies, highlighting the essential role of Tet2 in cellular transformation. However, the factors that control Tet enzymatic activity remain largely unknown. Here, we found that methyl-CpG-binding domain protein 3 (MBD3) and its homolog MBD3-like 2 (MBD3L2) can specifically modulate the enzymatic activity of Tet2 protein, but not Tet1 and Tet3 proteins, in converting 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC). Moreover, MBD3L2 is more effective than MBD3 in promoting Tet2 enzymatic activity through strengthening the binding affinity between Tet2 and the methylated DNA target. Further analysis revealed pronounced decreases in 5mC levels at MBD3L2 and Tet2 co-occupied genomic regions, most of which are promoter elements associated with either cancer-related genes or genes involved in the regulation of cellular metabolic processes. Our data add new insights into the regulation of Tet2 activity by MBD3 and MBD3L2, and into how that affects Tet2-mediated modulation of its target genes in cancer development. Thus, they ha...Continue Reading

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Citations

Jul 29, 2016·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Jie CuiLuo Gu
Jan 24, 2019·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Chuan ZhouYong Zhang
Aug 9, 2019·Cellular Reprogramming·Xingwang WangZicong Li
Dec 24, 2019·Journal of Clinical Laboratory Analysis·Zijing ZhangQiang Zou
Feb 24, 2019·Genome Research·Kasper D RasmussenKristian Helin
Jan 11, 2019·Nature Communications·James E LongbothamDanica Galonić Fujimori
Aug 17, 2021·Frontiers in Immunology·Wanhai QinTom van der Poll
Apr 15, 2020·Journal of the American Chemical Society·Shubhendu PaleiDaniel Summerer

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