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Homo sapiens

ABSTRACT: Methyl-CpG-binding domain (MBD) sequencing of 45 primary neuroblastoma tumors

PROVIDER: PRJNA285052 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR2040860_1.fastq.gz	Fastqsanger.gz
	SRR2040860_2.fastq.gz	Fastqsanger.gz
	SRR2040870_1.fastq.gz	Fastqsanger.gz
	SRR2040870_2.fastq.gz	Fastqsanger.gz
	SRR2040880_1.fastq.gz	Fastqsanger.gz

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Methyl-CpG-binding domain (MBD) sequencing of 45 primary neuroblastoma tumors

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Methyl-CpG-binding domain (MBD) sequencing of 45 primary neuroblastoma tumors

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Project description:In order to gain insight into DNA methylation readout, we have established a controlled strategy for profiling genomic targeting of chromatin-interacting factors in vivo. With this approach we determined binding preferences for the methyl-CpG binding domain (MBD) family of proteins, including disease relevant mutants, deletions and isoforms. In vivo binding of MBD proteins occurs as a linear function of local methylation density, and is dependent on functional MBD domain M-bM-^@M-^S methyl-CpG interactions. This directs specificity of MBD proteins to methylated, CpG dense and inactive regulatory regions. In contrast, binding to unmethylated sites is MBD protein specific and mediated via alternative domains or protein-protein interactions. The latter is observed for NuRD complex-mediated MBD2 tethering to a subset of unmethylated, tissue-specific regulatory regions, similar to MBD3. These functional binding maps reveal methylation-dependent and -independent binding modes determined by distinct protein domains and revise current models of DNA methylation readout through MBD proteins. Comparative binding analysis for the MBD family of proteins utilizing recombinase-assisted mapping of biotin-tagged proteins (RAMBiO). This set contains maps for 29 samples including wild type MBD proteins, mutants and domain variants in mouse ES cells, derived neurons (NP and TN) and Dnmt1/3a/3b triple-KO ES cells (TKO).

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