Biology subjects

Peng, F.

Publications and source records attributed to Peng, F..

44 records · Page 3Linked to original sources

bioRxiv2021

The anterior Hox gene ceh-13 and elt-1/GATA activate the posterior Hox genes nob-1 and php-3 to specify posterior lineages in the C. elegans embryo

Hox transcription factors play a conserved role in specifying positional identity during animal development, with posterior Hox genes typically repressing the expression of more anterior Hox genes. Here, we dissect the regulation of the posterior Hox genes nob-1 and php-3 in the nematode C. elegans. We show that nob-1 and php-3 are co-expressed in gastrulation-stage embryos in cells that previously expressed the anterior Hox gene ceh-13. This expression is controlled by several partially redundant transcriptional enhancers. These enhancers require ceh-13 for expression, providing a striking example of an anterior Hox gene positively regulating a posterior Hox gene. Several other regulators also act positively through nob-1/php-3 enhancers, including elt-1/GATA, ceh-20/ceh-40/Pbx, unc-62/Meis, pop-1/TCF, ceh-36/Otx and unc-30/Pitx. We identified defects in both cell position and cell division patterns in ceh-13 and nob-1;php-3 mutants, suggesting that these factors regulate lineage identity in addition to positional identity. Together, our results highlight the complexity and flexibility of Hox gene regulation and function and the ability of developmental transcription factors to regulate different targets in different stages of development. Author SummaryHox genes are critical for head-to-tail patterning during embryonic development in all animals. Here we examine the factors that are necessary to turn on two posterior Hox genes, nob-1 and php-3, in the nematode worm, C. elegans. We identified six new transcription factors and three enhancer regions of DNA that can activate expression of nob-1/php-3. Unexpectedly, these activating transcription factors included ceh-13, an anterior Hox gene, and elt-1, a regulator of skin development that is briefly expressed in many cells that do not adopt skin fates, including the cells that express nob-1. Furthermore, the cellular defects we observed in ceh-13 and nob- 1;php-3 mutant embryos indicate that the early embryonic functions of these Hox genes help determine the identity of cells as well as their position within the embryo. Our findings identify new roles for Hox genes in C. elegans and emphasize the ability of transcription factors to contribute to the diversification of cell types and the adoption of specific cell types at different phases of embryonic development.

genetics↗

bioRxiv2020

What evolutionary processes maintain MHCIIβ diversity within and among populations of stickleback?

Major Histocompatibility Complex (MHC) genes encode for proteins that recognize foreign protein antigens to initiate T-cell mediated adaptive immune responses. They are often the most polymorphic genes in vertebrate genomes. How evolution maintains this diversity is still an unsettled issue. Three main hypotheses seek to explain the maintenance of MHC diversity by invoking pathogen-mediated selection: heterozygote advantage, frequency-dependent selection, and fluctuating selection across landscapes or through time. Here, we use a large-scale field parasite survey in a stickleback metapopulation to test predictions derived from each of these hypotheses. We identify over a thousand MHCII{beta} alleles and find that many of them covary positively or negatively with parasite load, suggesting that these genes contribute to resistance or susceptibility. However, despite our large sample-size, we find no evidence for the widely-cited stabilizing selection on MHC heterozygosity, in which individuals with an intermediate number of MHC alleles have the lowest parasite burden. Nor do we observe a rare-allele advantage, or widespread fluctuating selection across populations. In contrast, we find that MHC diversity is best predicted by neutral genome-wide heterozygosity and between-population genomic divergence, suggesting neutral processes are important in shaping the pattern of metapopulation MHC diversity. Thus, although MHCII{beta} is highly diverse and relevant to the type and intensity of macroparasite infection in these populations of stickleback, the main models of MHC evolution still provide little explanatory power in this system.

evolutionary biology↗

bioRxiv2020

DORGE: Discovery of Oncogenes and Tumor SuppressoR Genes Using Genetic and Epigenetic Features

Comprehensive data-driven discovery of cancer driver genes, including tumor suppressor genes (TSGs) and oncogenes (OGs), is imperative for cancer prevention, diagnosis, and treatment. Although epigenetic alterations are important contributors to tumor initiation and progression, most known driver genes were identified based on genetic alterations alone, and it remains unclear to what the extent epigenetic features would facilitate the identification and characterization of cancer driver genes. Here we developed a prediction algorithm DORGE (Discovery of Oncogenes and tumor suppressoR genes using Genetic and Epigenetic features), which integrates the most comprehensive collection of tumor genetic and epigenetic data to identify TSGs and OGs, particularly those with rare mutations. DORGE identified histone modifications as strong predictors for TSGs, and it found missense mutations, super enhancer percentages, and methylation differences between cancer and normal samples as strong predictors for OGs. We extensively validated novel cancer driver genes predicted by DORGE using independent functional genomics data. We also found that the dual-functional genes, which are both TSGs and OGs predicted by DORGE, are enriched at hubs in protein-protein interaction and drug-gene networks. Overall, our study has deepened the understanding of epigenetic mechanisms in tumorigenesis and revealed a previously undetected repertoire of cancer driver genes.

bioinformatics↗

bioRxiv2019

Genetic Basis of Alternative Polyadenylation is an Emerging Molecular Phenotype for Human Traits and Diseases

Genome-wide association studies have identified thousands of non-coding variants that are statistically associated with human traits and diseases. However, functional interpretation of these variants remains a major challenge. Here, we describe the first atlas of human 3-UTR alternative polyadenylation (APA) Quantitative Trait Loci (3QTLs), i.e. [~]0.4 million genetic variants associated with APA of target genes across 46 Genotype-Tissue Expression (GTEx) tissues from 467 individuals. APA occurs in approximately 70% of human genes and substantively impacts cellular proliferation, differentiation and tumorigenesis. Mechanistically, 3QTLs could alter polyA motifs and RNA-binding protein binding sites, leading to thousands of APA changes. Importantly, 3QTLs can be used to interpret [~]16.1% of trait-associated variants and are largely distinct from other QTLs such as eQTLs. The genetic basis of APA (3QTLs) thus represent a novel molecular phenotype to explain a large fraction of non-coding variants and to provide new insights into complex traits and disease etiologies.\n\nHighlightsO_LIThe first atlas of human 3QTLs: [~]0.4 million genetic variants associated with alternative polyadenylation of target genes across 46 tissues from 467 individuals\nC_LIO_LI3QTLs could alter polyA motifs and RNA-binding protein binding sites\nC_LIO_LI3QTLs can be used to interpret [~]16.1% of trait-associated variants\nC_LIO_LIMany disease-associated 3QTLs contribute to phenotype independent of gene expression\nC_LI

bioinformatics↗

bioRxiv2019

Quantitative proteomic profiling of tumor-associated vascular endothelial cells in colorectal cancer

SummeryTo investigate the global proteomic profiles of vascular endothelial cells (VECs) in the tumor microenvironment and antiangiogenic therapy for colorectal cancer (CRC), matched pairs of normal (NVECs) and tumor-associated VECs (TVECs) were purified from CRC tissues by laser capture microdissection and subjected to iTRAQ based quantitative proteomics analysis. Here, 216 differentially expressed proteins (DEPs) were identified and performed bioinformatics analysis. Interestingly, these proteins were implicated in epithelial mesenchymal transition (EMT), ECM-receptor interaction, focal adhesion, PI3K-Akt signaling pathway, angiogenesis and HIF-1 signaling pathway, which may play important roles in CRC angiogenesis. Among these DEPs, Tenascin-C (TNC) was found to upregulated in the TVECs of CRC and be correlate with CRC multistage carcinogenesis and metastasis. Furthermore, the reduction of tumor-derived TNC could attenuate human umbilical vein endothelial cell (HUVEC) proliferation, migration and tube formation through ITGB3/FAK/Akt signaling pathway. Based on the present work, we provided a large-scale proteomic profiling of VECs in CRC with quantitative information, a certain number of potential antiangiogenic targets and a novel vision in the angiogenesis bio-mechanism of CRC. Summery statementWe provided large-scale proteomic profiling of vascular endothelial cells in colorectal cancer with quantitative information, a number of potential antiangiogenic targets and a novel vision in the angiogenesis bio-mechanism of CRC.

cancer biology↗

bioRxiv2018

Formation of periodic pigment spots by the reaction-diffusion mechanism

Many organisms exhibit visually striking spotted or striped pigmentation patterns. Turings reaction-diffusion model postulates that such periodic pigmentation patterns form when a local autocatalytic feedback loop and a long-range inhibitory feedback loop interact. At its simplest, this network only requires one self-activating activator that also activates a repressor, which inhibits the activator and diffuses to neighboring cells. However, the molecular activators and repressors fully fitting this versatile model remain elusive. Here, we characterize an R2R3-MYB activator and an R3-MYB repressor in monkeyflowers that correspond to Turings model and explain how periodic anthocyanin spots form. Notably, disrupting this pattern impacts pollinator visitation. Thus, subtle changes in simple reaction-diffusion networks are likely essential contributors to the evolution of the remarkable diversity of periodic pigmentation patterns in flowers.

plant biology↗

bioRxiv2018

Conflict of evolutionary interests between plants and pollinators revealed through functional exploration of flower morphospace

The explosive evolutionary diversification of flowering plants traditionally is attributed to the coevolution of plants and their animal pollinators. Plant-pollinator interactions are held as classical examples of mutualisms - beneficial to both parties - in spite of the fact that most other cases of rapid coevolution are the result of conflicts of interest (e.g., predator-prey, host-parasite, sexual conflict, competition for resources). Could the co-diversification of plants and their pollinators be driven by conflict rather than by mutualism? To address this question, we employed the theoretical morphospace paradigm using a combination of 3D printing, electronic sensing, and machine vision technologies to determine the influence of two flower morphological features (corolla curvature and nectary diameter) on the fitness of both parties: the artificial flower and its hawkmoth pollinator. We found that the two parties have almost opposite interests in corolla curvature evolution, with non-overlapping fitness peaks in flower morphospace, suggesting that the evolutionary radiation of flowering plants and their pollinators could be the result of conflict instead of mutualism.

ecology↗

bioRxiv2018

Small-scale soil microbial community heterogeneity linked to landforms on King George Island, maritime Antarctica

We analysed soil-borne microbial (bacterial, archaeal, and fungal) communities around the Fildes Region of King George Island, maritime Antarctica, which were divided into two groups according to soil elemental compositions and environmental attributes (soil chemical parameters and vegetation conditions) located in Holocene raised beach and Tertiary volcanic stratigraphy. Prokaryotic communities of the two groups were well separated; they predominantly correlated with soil elemental compositions, and were secondly correlated with environmental attributes (e.g., soil pH, total organic carbon, [Formula], and vegetation coverage; Pearson test, r = 0.59 vs. 0.52, both P < 0.01). The relatively high abundance of P, S, Cl, and Br in Group 1 was likely due to landform uplift. Lithophile-elements (Si, Al, Ca, Sr, Ti, V, and Fe) correlated with prokaryotic communities in Group 2 may originate from weathering of Tertiary volcanic rock. The elements and nutrients accumulated during formation of different landforms influenced the development of soils, plant growth, and microbial communities, and resulted in small-scale spatially heterogeneous biological distributions. We propose that the geological evolution of the Fildes Region was crucial to its microbial community development.\n\nIMPORTANCEThis current study analyzed soil-borne microbial communities around the Fildes Region of King George Island, maritime Antarctica, which were divided into two groups according to soil elemental compositions and environmental attributes. We provide new evidence for the crucial influence of landforms on small-scale structures and spatial heterogeneity of soil microbial communities.

microbiology↗