Project description:To investigate the effect of supergene status and social environment pre- and post-pupation, we used RNA-sequencing of fire ant ant workers to assess gene expression differences.
Project description:The goal of this study was to assay the extent of variation in chromatin organization between 3 ant castes (major and minor female workers and males) in one colony of Camponotus floridanus carpenter ant using ChIPseq. 45 samples total: 30 ChIP samples and 3 inputs for total histone H3, 7 histone H3 PTMs and RNA Pol II in major, minor, and male ants; CBP in major and minor ants; the major H3K27ac sample was replicated. 4 ChIP samples for H3 and H3K27ac in brains of majors and minors, and 2 inputs. 2 RNAseq samples for major and minor ants head+thorax; 4 RNAseq samples for brain (majors and minors with 2 replicates each).
Project description:High tumor mutational burden (TMB) is a predictive biomarker for the responsiveness of cancer to immune checkpoint inhibitor therapy that indicates whether immune cells can sufficiently recognize cancer cells as non-self. However, about 30% of all cancers from The Cancer Genome Atlas are classified as immune-desert tumors lacking T cell infiltration despite high TMB. Since the underlying mechanism of these immune-desert tumors has yet to be unraveled, there is a pressing need to transform such immune-desert tumors into immune-inflamed tumors and thereby enhance their responsiveness to anti-PD1 therapy. Here, we present a systems framework for identifying immuno-oncotargets, based on analysis of gene regulatory networks, and validating the effect of these targets in transforming immune-desert into immune-inflamed tumors. In particular, we identify DEAD-box helicases 54 (DDX54) as a master regulator of immune escape in immune-desert lung cancer with high TMB, and show that knockdown of DDX54 can increase immune cell infiltration and lead to improved sensitivity to anti-PD1 therapy.
Project description:The goal of this study was to assay the extent of variation in chromatin organization between 3 ant castes (major and minor female workers and males) in one colony of Camponotus floridanus carpenter ant using ChIPseq.
Project description:Gene deserts spanning more than 500kb of non-protein coding genomic sequence are considered evolutionarily ancient and stable and are enriched in the vicinity of developmental regulator genes (Ovcharenko 2005). These extensive genomic regions typically harbor numerous conserved elements with predicted gene regulatory potential pointing to critical tissue-specific functions during development. Nevertheless, the biological necessity and underlying funtional enhancer landscapes of most gene deserts near developmental transcription factors (TFs) remain unknown, and it is unclear how precise pleiotropic expression patterns emerge from gene desert sequence. Here, we investigated the cis-regulatory architecture and function of a gene desert flanking the mouse Shox2 transcriptional regulator which itself is essential for embryonic limb, craniofacial, and cardiac pacemaker development. By combining epigenomic enhancer prediction, transgenic reporter validation and region-specific chromatin capture (C-HiC), we define the embryonic in vivo enhancer landscape and chromatin topology of the Shox2 gene desert. Targeted and context-specific genomic deletions uncover the gene desert not only as a regulator of embryonic survival through enhancer-mediated control of cardiac Shox2 expression, but also link distinct subsets of tissue-specific gene desert enhancers to the regulation of craniofacial patterning and proximal limb development. Our results hence identify the Shox2 gene desert as a fundamental genomic unit indispensable for pleiotropic patterning, robust organ morphogenesis and embryonic development progression by serving as a dynamic hub for tissue-specific developmental enhancers.
Project description:Gene deserts spanning more than 500kb of non-protein coding genomic sequence are considered evolutionarily ancient and stable and are enriched in the vicinity of developmental regulator genes (Ovcharenko 2005). These extensive genomic regions typically harbor numerous conserved elements with predicted gene regulatory potential pointing to critical tissue-specific functions during development. Nevertheless, the biological necessity and underlying funtional enhancer landscapes of most gene deserts near developmental transcription factors (TFs) remain unknown, and it is unclear how precise pleiotropic expression patterns emerge from gene desert sequence. Here, we investigated the cis-regulatory architecture and function of a gene desert flanking the mouse Shox2 transcriptional regulator which itself is essential for embryonic limb, craniofacial, and cardiac pacemaker development. By combining epigenomic enhancer prediction, transgenic reporter validation and region-specific chromatin capture (C-HiC), we define the embryonic in vivo enhancer landscape and chromatin topology of the Shox2 gene desert. Targeted and context-specific genomic deletions uncover the gene desert not only as a regulator of embryonic survival through enhancer-mediated control of cardiac Shox2 expression, but also link distinct subsets of tissue-specific gene desert enhancers to the regulation of craniofacial patterning and proximal limb development. Our results hence identify the Shox2 gene desert as a fundamental genomic unit indispensable for pleiotropic patterning, robust organ morphogenesis and embryonic development progression by serving as a dynamic hub for tissue-specific developmental enhancers.
Project description:Variation in continuous traits, such as height, is a complex output of genetic and environmental factors. In the Florida carpenter ant, workers are 75% genetically related but exhibit a wide range of lengths that broadly categorizes them into minor or major subcastes with specific roles within the colony. While initial studies have suggested that epigenetic changes can mediate the influence of the environment in the differential development of minor and major ants, no study has comprehensively studied ant size as a continuous phenotype with genome-wide approaches. Here, we exploit the entire continuous spectrum of ant size, mRNA expression, microRNA expression, and DNA methylation – in combination with genomic sequencing – to identify the molecular and epigenetic factors driving the determination of body size. We report dramatic changes in gene expression in key genes linked to sugar metabolism as well as the correlation of expression of a large proportion of the transcriptome to size, involving pathways related to DNA replication, muscle growth, and neuronal development. We further identify and investigate the correlation of the expression of microRNAs and levels of DNA methylation with size, as well as their link to histone modifications, which together, might sculpt differential gene expression profiles. Together, this study unveils a coordinated molecular and epigenetic regulatory network determining body size, offering valuable insights into developmental biology and the molecular contributions to body size in the context of C. floridanus and beyond.
Project description:The study evaluated the differential gene expression in control Antibody or Ant-CXCL10 antibody injected mouse when compared to EZH2 inhibitor GSK343 treated mice tumors Briefly, control Antibody or Ant-CXCL10 antibody injected C57BL/6 mouse were treated with or without GSK343were analyzed for RNA-seq