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Mus musculus

ABSTRACT: DNMT3B overexpression contributes to aberrant DNA methylation and MYC-driven tumor maintenance in T-ALL and Burkitt’s lymphoma

PROVIDER: PRJNA395905 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR5870980.fastq.gz	Fastqsanger.gz
	SRR5870979.fastq.gz	Fastqsanger.gz

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DNMT3B7 disrupts embryonic development and accelerates lymphomagenesis

Project description:Cancer cells have an altered distribution of DNA methylation and express aberrant DNA methyltransferase 3B transcripts, which encode truncated proteins. To test if a truncated DNMT3B isoform disrupts DNA methylation in vivo, we constructed transgenic mice expressing DNMT3B7, a common truncated DNMT3B isoform in cancer cells. DNMT3B7 transgenic mice exhibit altered embryonic development, including lymphopenia, craniofacial abnormalities, and cardiac defects, similar to Dnmt3b-deficient animals, but rarely develop cancer. However, DNMT3B7 expression increases the frequency of mediastinal lymphomas in Eμ−myc animals. Eμ-myc/DNMT3B7 lymphomas have more chromosomal rearrangements, increased global methylation levels, and more locus-specific perturbations in DNA methylation patterns compared to Eμ-myc lymphomas. Our results demonstrate that a truncated DNMT3B protein can alter tumorigenesis, suggesting a similar role in human tumors. Direct comparison of DNA methylation in lymphoma samples from Eu-Myc vs Eu-Myc/Dnmt3b7 mice.

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DNMT3B overexpression contributes to aberrant DNA methylation and MYC-driven tumor maintenance in T-ALL and Burkitt’s lymphoma

Project description:We performed methylation profiling using RRBS-seq to investigate the role of DNMT3B in MYC-driven tumor maintenance. Comparing tumor cells before and upon DNMT3B knock-down revealed genome-wide changes in the DNA methylation pattern.

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