The overarching goal of our lab is to understand the mechanism and function of programmed DNA elimination, a unique form of DNA loss, chromosome end remodeling, and gene silencing. Genome integrity and its maintenance are essential to an organism. Although genome changes can enable variation, flexibility, and evolution, large-scale genome changes, such as chromosome breaks and DNA loss are often detrimental to organisms and lead to diseases, including cancer. However, regulated chromosome breaks and DNA loss is a physiological process during early development in a few organisms, including some parasitic nematodes (intestinal worms) and copepods (small crustaceans). This large-scale DNA loss is known as programmed DNA elimination. DNA elimination occurs only in somatic cells, not the germline, leading to a smaller somatic genome. Our previous studies demonstrated that in the nematode Ascaris, ~1,000 germline-expressed genes are lost during DNA elimination, suggesting that DNA elimination is a novel form of gene silencing in somatic cells.
We are using the nematode Ascaris and copepod Mesocyclops edax as model systems, to try to address outstanding questions related to DNA elimination, including 1). How are the break sites recognized and defined? 2). How are the DNA double-stranded breaks made? 3). How are the DNA break ends processed and repaired? and 4). How is the eliminated DNA degraded? Our lab is using specialized genome technologies, including END-seq to identify DNA breaks, PRO-seq to define nascent transcription, DRIP-seq to determine R-loop formation, and Hi-C to map 3D genome interactions, as well as common genomics approaches (genome sequences, RNA-seq, ChIP-seq, and ATAC-seq) to study chromosomes and chromatin organization, RNA transcription, DNA replication, DNA breaks and telomere healing that are related to programmed DNA elimination. DNA break and repair mechanisms are essential to genome stability and maintenance. Understanding the physiological process of the DNA elimination may provide novel insights into DNA break and repair mechanisms that may facilitate a better understanding of DNA break and loss in diseases.
Ph.D. Bioinformatics, Zhejiang University, Hangzhou, China
Wang J, Davis RE: Ascaris. Current Biology 2020, 30:R1-3
Wang J*, Gao S, Mostovoy Y, Kang Y, Zagoskin M, Sun Y, Zhang B, White LK, Easton A, Nutman TB, Kwok PY, Hu S, Nielsen MK, Davis RE*: Comparative Genome Analysis of Programmed DNA Elimination in Nematodes. (*Corresponding authors). Genome Research 2017, 27:2001-14
Kang Y*, Wang J*, Neff A, Kratzer S, Kimura H and Davis RE. Differential Chromosomal Localization of Centromeric Histone CENP-A Contributes to Nematode Programmed DNA Elimination. Cell Reports, 2016, 16: 2308-2316 (* Co-first author).
Wang J*, Garrey J*, Davis RE: Transcription in pronuclei and one- to four-cell embryos drives early development in a nematode. Current Biology 2014, 24:124-133. (* These authors contributed equally)
Wang J*, Davis RE*: Programmed DNA elimination in multicellular organisms. Current Opinion in Genetics & Development 2014, 27:26-34. (* Corresponding authors)
Wang J, Mitreva M, Berriman M, Thorne A, Magrini V, Koutsovoulos G, Kumar S, Blaxter ML, Davis RE: Silencing of germline-expressed genes by DNA elimination in somatic cells. Developmental Cell 2012, 23:1072-1080.
Wang J, Czech B, Crunk A, Wallace A, Mitreva M, Hannon GJ, Davis RE: Deep small RNA sequencing from the nematode Ascaris reveals conservation, functional diversification, and novel developmental profiles. Genome Research 2011, 21:1462-1477.