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Tracing Mitotic Division History with Genome-wide DNA Methylation Loss

Wednesday, January 22, 2020

4:00 PM-5:30 PM

BIOMED Seminar

Tracing Mitotic Division History with Genome-wide DNA Methylation Loss

Wanding Zhou, PhD
Assistant Professor
Children's Hospital of Philadelphia (CHOP)
University of Pennsylvania

Global loss of DNA methylation is a signature epigenetic feature of human cancer, and its therapeutic induction leads to tumor growth inhibition and apoptosis. DNA methylation loss preferentially happens to genomic territories that are lamina-associated and late in DNA replication. We analyzed sequence preference of DNA methylation loss in a wide range of cancer types and found that CpGs in the context of low CpG density and the WCGW tetranucleotide context (“solo-WCGW” CpGs) are most prone to loss of methylation.

Analysis of these solo-WCGW CpGs allowed for more sensitive detection of methylation loss in nonmalignant samples, revealing an almost unanimous existence of methylation loss across a wide range of the normal somatic developmental lineages in both human and mouse. This loss can be traced back to early embryonic development and appears to track the cumulative number of cell divisions, likely behaving as a mitotic clock akin to telomere shortening. This conjecture is supported by the association of methylation loss with chronological age, somatic mutation density in cancer, and transcriptional activity in cell-replication machinery in large population studies.

This seminar features the introduction of DNA methylation loss with a discussion of its cellular origin, developmental footprint, implication to cancer incidence and disease predisposition.

Wanding Zhou, PhD, is an assistant professor at The Children’s Hospital of Philadelphia and The University of Pennsylvania. He received his PhD in Bioengineering from Rice University in 2013. After that, Dr. Zhou became an Odyssey Fellow at the University of Texas MD Anderson Cancer Center and a postdoc at Van Andel Research Institute. He currently leads the Lab of Computational Epigenetics at CHOP in the Center for Computational and Genomic Medicine. His lab focuses on the Bioinformatics for DNA methylation.

Dr. Zhou's past and ongoing work is aimed at understanding the structure and cellular origin of DNA methylation alterations during organismal development and disease progression. He is the lead author of multiple bioinformatics tools for DNA methylation, including TransVar, BISCUIT, and SeSAMe.

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