MassIVE MSV000091764

Partial Public PXD041712

The TDG interactome connects active DNA demethylation with chromatin and RNA biology

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Description

Controlled gene expression requires the crosstalk of different chromatin-targeted mechanisms to regulate the accessibility and configuration of the genome for transcription. Dynamic DNA methylation is of them, but its role in chromatin organization is poorly understood. We set out to explore the functional space of the DNA glycosylase and demethylase TDG in mouse embryonic stem cells (mESCs). Taking advantage of the unbiased proximity ligation method (BIOID2), we discovered a series of novel TDG interacting partners relating to functions beyond DNA bases excision repair. We identified proteins functionally involved in chromatin remodeling, such as RUVBL2 and SMARCA4, and also with HCFC1, which has been shown to tether the histone methyltransferase MLL complex to important regulatory sites. Moreover, we could discover a new role of TDG with RNA-binding proteins and demonstrate that TDG is associated with the paraspeckle components, including the noncoding RNA Neat1. Its ability to associate with several noncoding RNAs and process DNA in R-loops suggests a function of such structures in regulating active DNA demethylation. [doi:10.25345/C5GM81Z8X] [dataset license: CC0 1.0 Universal (CC0 1.0)]

Keywords: Active DNA demethylation ; TDG ; chromatin and epigenetics ; RNA biology ; BIOID2 method ; mouse embryonic stem cells

Contact

Principal Investigators:
(in alphabetical order) 		Alexander Schmidt, Biozentrum, Universtiy of Basel, 4056 Basel, Switzerland, N/A
Submitting User: katarzynabuczak
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