Biology subjects

Mao, F.

Publications and source records attributed to Mao, F..

3 recordsLinked to original sources

bioRxiv2017

PPARD regulation in gastric progenitor cells drives gastric tumorigenesis in mice

Little is known about the cell origin of gastric cancer. Peroxisome proliferator-activated receptor-delta (PPARD) is a druggable ligand-activated nuclear receptor that impacts protumorigenic cellular events. However, PPARDs role in tumorigenesis, especially gastric tumorigenesis, remains to be defined. We found that targeting PPARD overexpression in murine gastric progenitor cells (GPC), via a villin promoter, spontaneously induced gastric tumorigenesis that progressed to invasive adenocarcinoma. PPARD overexpression in GPC upregulated tumorigenic proinflammatory cytokine and CD44 expression, expanded GPC population in vivo, enhanced GPC self-renewal and proliferation in organoid cultures, and endowed these cells with tumorigenic properties. Our findings identify PPARD as a driver of gastric tumorigenesis via GPC transformation.

cancer biology↗

bioRxiv2017

Phytophthora methylomes modulated by expanded 6mA methyltransferases are associated with adaptive genome regions

Filamentous plant pathogen genomes often display a bipartite architecture with gene sparse, repeat-rich compartments serving as a cradle for adaptive evolution. However, the extent to which this \"two-speed\" genome architecture is associated with genome-wide epigenetic modifications is unknown. Here, we show that the oomycete plant pathogens Phytophthora infestans and Phytophthora sojae possess functional adenine N6- methylation (6mA) methyltransferases that modulate patterns of 6mA marks across the genome. In contrast, 5-methylcytosine (5mC) could not be detected in the two Phytophthora species. Methylated DNA IP Sequencing (MeDIP-seq) of each species revealed that 6mA is depleted around the transcriptional starting sites (TSS) and is associated with low expressed genes, particularly transposable elements. Remarkably, genes occupying the gene-sparse regions have higher levels of 6mA compared to the remainder of both genomes, possibly implicating the methylome in adaptive evolution of Phytophthora. Among three putative adenine methyltransferases, DAMT1 and DAMT3 displayed robust enzymatic activities. Surprisingly, single knockouts of each of the 6mA methyltransferases in P. sojae significantly reduced in vivo 6mA levels, indicating that the three enzymes are not fully redundant. MeDIP-seq of the damt3 mutant revealed uneven patterns of 6mA methylation across genes, suggesting that PsDAMT3 may have a preference for gene body methylation after the TSS. Our findings provide evidence that 6mA modification is an epigenetic mark of Phytophthora genomes and that complex patterns of 6mA methylation by the expanded 6mA methyltransferases may be associated with adaptive evolution in these important plant pathogens.

molecular biology↗

bioRxiv2017

De novo mutations involved in post-transcriptional dysregulation contribute to six neuropsychiatric disorders

While deleterious de novo mutations (DNMs) in coding region conferring risk in neuropsychiatric disorders have been revealed by next-generation sequencing, the role of DNMs involved in post-transcriptional regulation in pathogenesis of these disorders remains to be elucidated. Here, we identified 1,736 post-transcriptionally impaired DNMs (piDNMs), and prioritized 1,482 candidate genes in four neuropsychiatric disorders from 7,748 families. Our results revealed higher prevalence of piDNMs in the probands than in controls (P = 8.19x10-17), and piDNM-harboring genes were enriched for epigenetic modifications and neuronal or synaptic functions. Moreover, we identified 86 piDNM-containing genes forming convergent co-expression modules and intensive protein-protein interactions in at least two neuropsychiatric disorders. These cross-disorder genes carrying piDNMs could form interaction network centered on RNA binding proteins, suggesting a shared post-transcriptional etiology underlying these disorders. Our findings illustrate the significant contribution of piDNMs to four neuropsychiatric disorders, and lay emphasis on combining functional and network-based evidences to identify regulatory causes of genetic disorders.

genomics↗