The African trypanosome Trypanosoma brucei is a single-celled eukaryotic protozoan parasite with a single cilium/flagellum. It cycles between its mammalian host (bloodstream cell), in which it scavenges cholesterol, and its tsetse fly host (procyclic cell), in which it both scavenges cholesterol and synthesizes ergosterol. For the first part of the...
FOXA1 is a FKHD family protein that plays pioneering roles in lineage-specific enhancer activation and gene transcription. Through genome-wide location analyses, here we show that FOXA1 expression and occupancy are, in turn, required for the maintenance of these epigenetic signatures, namely DNA hypomethylation and histone 3 lysine 4 methylation. Mechanistically,...
The polypeptide hormone prolactin (PRL) is increasingly recognized as contributing to the development and progression of human breast cancer. This is supported by epidemiologic studies that found women with high levels of serum PRL are at an increased risk for developing breast cancer. Activation of the prolactin receptor (PRLR) by...
Radiation is a ubiquitous health risk. Contemporary populations are exposed to several hundred milliSieverts per person over their lifetimes from both natural and human made sources such as radon, cosmic rays, CT-scans, etc. Risk estimates based on studies of atomic bomb survivors suggest that these exposures induce excess cancer mortality...
Kainate receptors (KARs) are expressed throughout the central and peripheral nervous systems. One of three subfamilies of ionotropic glutamate receptors, KARs are localized both pre- and post-synaptically and exert important modulatory control over neural circuits. This modulatory role in circuit function makes them a potential actor in wide variety of...
The airway epithelium forms an active barrier between the internal and external environments and has multiple roles critical to normal function of the lung. Its development and function are controlled by a network of transcription factors that regulate gene expression in response to varying stimuli. Dysfunction of this tissue plays...
CD1 molecules represent a class of antigen presenting molecules that present lipid antigens to cognate T cells. These molecules have been identified in all mammals examined so far. Unlike MHC molecules, which are highly polymorphic, CD1 molecules exhibit limited polymorphism and are divided in to two groups – 1 and...
Gene expression is tightly regulated at the level of transcription through cooperation between cis-regulatory elements and trans-factors that bind to the regulatory elements. Together, these factors regulate the higher order chromatin structure which establishes domains that organize the genome and coordinate gene expression. However, the molecular mechanisms controlling transcription of...
E2F-2 is a Retinoblastoma (Rb)-regulated transcription factor induced during terminal erythroid maturation. Cyclin E-mediated Rb hyper-phosphorylation induces E2F transcriptional activator functions. E2F-2-loss causes reduced peripheral red blood cell (RBC) counts, without altering relative abundances of erythroblast subpopulations. To determine how E2F-2 regulates RBC production, we comprehensively studied erythropoiesis using knockout...