Genomics and Proteomics
- A new form of somatic gene recombination (SGR) has been identified in the human brain that affects the Alzheimer's disease gene, amyloid precursor protein (APP). SGR occurs when a gene sequence is cut and recombined within a single cell's genomic DNA, generally independent of DNA replication and the cell cycle. The newly identified brain SGR produces genomic complementary DNAs (gencDNAs) lacking introns, which integrate into locations distinct from germline loci. This brief review will present an overview of likely related recombination mechanisms and genomic cDNA-like sequences that implicate evolutionary origins for brain SGR.
- Platinum-based chemotherapies, including oxaliplatin, are a mainstay in the management of solid tumors and induce cell death by forming intrastrand dinucleotide DNA adducts. Despite their common use, they are highly toxic, and approximately half of cancer patients have tumors that are either intrinsically resistant or develop resistance. Previous studies suggest that this resistance is mediated by variations in DNA repair levels or net drug influx. Here, we aimed to better define the roles of nucleotide excision repair and DNA damage in platinum chemotherapy resistance by profiling DNA damage and repair efficiency in seven oxaliplatin-sensitive and three oxaliplatin-resistant colorectal cancer cell lines.
- The small, secreted peptide, insulin-like growth factor 2 (IGF2), is essential for fetal and prenatal growth in humans and other mammals. Human IGF2 and mouse Igf2 genes are located within a conserved linkage group and are regulated by parental imprinting, with IGF2/Igf2 being expressed from the paternally derived chromosome, and H19 from the maternal chromosome. Here, data retrieved from genomic and gene expression repositories were used to examine the Igf2 gene and locus in 8 terrestrial vertebrates, 11 ray-finned fish, and 1 lobe-finned fish representing >500 million years of evolutionary diversification.
- Recent advances in genetics present unique opportunities for enhancing knowledge about human physiology and disease susceptibility. Understanding this information at the individual gene level is challenging and requires extracting, collating, and interpreting data from a variety of public gene repositories. Here, I illustrate this challenge by analyzing the gene for human insulin-like growth factor 2 (IGF2) through the lens of several databases. IGF2, a 67-amino acid secreted peptide, is essential for normal prenatal growth and is involved in other physiological and pathophysiological processes in humans.
- The insulin-like growth factors IGF1 and IGF2 are closely related proteins that are essential for normal growth and development in humans and other species and play critical roles in many physiological and pathophysiological processes. IGF actions are mediated by transmembrane receptors and modulated by IGF-binding proteins. The importance of IGF actions in human physiology is strengthened by the rarity of inactivating mutations in their genes and by the devastating impact caused by such mutations on normal development and somatic growth.
- Gut microbiota play an important role in regulating the development of the host immune system, metabolic rate, and at times, disease pathogenesis. The factors and mechanisms that mediate interactions between microbiota and the intestinal epithelium are not fully understood. We provide novel evidence that microbiota may control intestinal epithelial stem cell (IESC) proliferation in part through microRNAs (miRNAs). We demonstrate that miRNA profiles differ dramatically across functionally distinct cell types of the mouse jejunal intestinal epithelium and that miRNAs respond to microbiota in a highly cell type-specific manner.
- The thalassospiramide lipopeptides have great potential for therapeutic applications; however, their structural and functional diversity and biosynthesis are poorly understood. Here, by cultivating 130 Rhodospirillaceae strains sampled from oceans worldwide, we discovered 21 new thalassospiramide analogues and demonstrated their neuroprotective effects. To investigate the diversity of biosynthetic gene cluster (BGC) architectures, we sequenced the draft genomes of 28 Rhodospirillaceae strains. Our family-wide genomic analysis revealed three types of dysfunctional BGCs and four functional BGCs whose architectures correspond to four production patterns.
- Recent work from others and us revealed interactions between the Sin3/HDAC complex, the H3K4me3 demethylase KDM5A, GATAD1, and EMSY. Here, we characterize the EMSY/KDM5A/SIN3B complex in detail by quantitative interaction proteomics and ChIP-sequencing. We identify a novel substoichiometric interactor of the complex, transcription factor ZNF131, which recruits EMSY to a large number of active, H3K4me3 marked promoters. Interestingly, using an EMSY knock-out line and subsequent rescue experiments, we show that EMSY is in most cases positively correlated with transcriptional activity of its target genes and stimulates cell proliferation.
- Background: Cyanobacteriochromes (CBCRs), photoreceptors that sense red to near-UV light, were not previously reported in the cyanobacterium Microcoleus.Results: The Microcoleus genome encodes seven CBCR proteins covalently attached to phycocyanobilin or phycoviolobilin.Conclusion: Near-UV and violet CBCRs are enriched in Microcoleus, whereas red- and green-sensitive CBCRs are absent.Significance: This is the first report of CBCRs in the Microcoleus genome.