Genomics

Dataset Information

53

The methyl binding domain 3 (MBD3) family proteins promote Tet2 enzymatic activity for mediating 5mC conversion [HTS]


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 MBD3 and its analogue MBD3L2 can specifically modulate the enzymatic activity of Tet2 protein, but not Tet1 and Tet3 proteins, in converting 5mC into 5hmC. Moreover, MBD3L2 is more effective than MDB3 in promoting Tet2 enzymatic activity via 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 in modulating its target gene activities in cancer development and have important applications in understanding how dysregulation of TET2 may contribute to human malignancy. Overall design: ChIP-Seq experiments were performed for HA-Tet2 and HA-MBD3L2 in HEK293T cells overexpressing these two proteins. Comparative hMeDIP-Seq experiments were conducted to compare the genome-wide distribution of 5hmC in HEK293T cells after transfection of Tet2 and MBD3L2 simultaneously or individually. RRBS experiments were used to detect the global methylation level change after transfection of Tet2 and MBD3L2.

INSTRUMENT(S): Illumina HiSeq 2000 (Homo sapiens)

SUBMITTER: Wei Li 

PROVIDER: GSE74914 | GEO | 2016-03-03

SECONDARY ACCESSION(S): PRJNA301900

REPOSITORIES: GEO

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Publications

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

Peng Lina L   Li Yan Y   Xi Yanping Y   Li Wei W   Li Jin J   Lv Ruitu R   Zhang Lei L   Zou Qingping Q   Dong Shihua S   Luo Huaibing H   Wu Feizhen F   Yu Wenqiang W  

Journal of cell science 20160114 5


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 ac  ...[more]

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