Project description:The protein-coding gene networks regulating heart development are well known. Less understood are the roles of long non-coding RNAs (lncRNAs), many of which are poorly conserved due to their origins from transposable elements (TEs) such as endogenous retroviruses (ERVs). Here, we report hundreds of ERV elements from the primate-specific MER41 family are expressed in pluripotent cell-derived cardiomyocytes and fetal heart, some of which are regulated by the cardiogenic transcription factor TBX5. The most significant of these are located within BANCR, an lncRNA exclusively expressed in primate fetal cardiomyocytes in normal physiology. Surprisingly, BANCR promotes cellular movement in fetal cardiomyocytes, which is due in part to Rho GTPase and ephrin receptor signaling. We postulate that ERV-derived BANCR is a recent evolutionary mechanism for enabling larger heart sizes in primates, and underscores the remarkable retroviral origins of humans.
Project description:The domestic ferret has recently been described as a uniformly lethal model of infection for three species of Ebolavirus known to be pathogenic to humans. Reagents to systematically analyze the ferret host response to infection are lacking; however, the recent publication of a draft ferret genome has opened the potential for transcriptional analysis of ferret models of disease. In this work, we present comparative analysis of longitudinally sampled blood taken from ferrets and non-human primates infected with lethal doses of the Makona strain of Zaire ebolavirus. Strong induction of proinflammatory and prothrombotic signaling programs were present in both ferrets and non-human primates and both transcriptomes were similar to previously published datasets of fatal cases of human Ebola virus infection.
Project description:Changes in gene regulation are thought to play an important role in speciation and adaptation, especially in primates. However, we still know relatively little about the mechanisms underlying regulatory evolution. In particular, the extent to which epigenetic modifications underlie gene expression differences between primates is not yet known. Our study focuses on an epigenetic histone modification, H3K4me3, which is thought to promote transcription. To investigate the contribution of H3K4me3 to regulatory differences between species, we collected gene expression data and identified H3K4me3-associated genomic regions in lymphoblastoid cell lines (LCLs) from humans, chimpanzees, and rhesus macaques, using three cell lines from each species. We found strong evidence for conservation of H3K4me3 localization in primates. Moreover, regardless of species, H3K4me3 is consistently enriched near annotated transcription start sites (TSS), and highly expressed genes are more likely than lowly expressed genes to have the histone modification near their TSS. Interestingly, we observed an enrichment of interspecies differences in H3K4me3 at the TSS of genes that are differentially expressed between species. We estimate that as much as 7% of gene expression differences between the LCLs of humans, chimpanzees, and rhesus macaques may be explained, at least in part, by changes in the status of H3K4me3 histone modifications. Our results suggest a modest, yet important role for epigenetic changes in gene expression differences between primates. Examination of H3K4me3 profiles in lymphoblastoid cell lines (LCLs) from three primate species (human, chimpanzee, and rhesus macaque), using 3 samples from each species, compared to a pooled input control from each species. Expression profiling was also done in the same LCL samples.
