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SnapShot: Root Development.
A Polymorphism in IRF4 Affects Human Pigmentation through a Tyrosinase-Dependent MITF/TFAP2A Pathway.
We demonstrate that this SNP lies within an enhancer of IRF4 transcription in melanocytes. The allele associated with this pigmentation phenotype impairs binding of the TFAP2A transcription factor that, together with the melanocyte master regulator MITF, regulates activity of the enhancer. Assays in...
Affinity Proteomics Reveals Human Host Factors Implicated in Discrete Stages of LINE-1 Retrotransposition.
We describe a system to express and purify highly active L1 RNP complexes from human suspension cell culture and characterize the copurified proteome, identifying 37 high-confidence candidate interactors. These data sets include known interactors PABPC1 and MOV10 and, with in-cell imaging studies, s...
T Cell Susceptibility to HIV Influences Outcome of Opportunistic Infections.
We examine how differences in the phenotype and function of pathogen-specific CD4 T cells influence susceptibility to HIV infection. By focusing on three common opportunistic infections (Mycobacterium tuberculosis, human papillomavirus, and cytomegalovirus), we investigate how differential depletion...
MEF2 is an in vivo immune-metabolic switch.
We use paired genetic and computational screens in Drosophila to identify transcriptional regulators of immunity and pathology and their associated target genes and physiologies. We show that Mef2 is required in the fat body for anabolic function and the immune response. Using genetic and biochemica...
The missing link between itch and inflammation in atopic dermatitis.
Atopic dermatitis is a common skin disease with high morbidity and is associated with severe itch and chronic skin inflammation. In this issue of Cell, Wilson et al. demonstrate that epithelial cells communicate directly with cutaneous sensory neurons via a cytokine to induce itch. Copyright © 2013...
Agonist-independent GPCR activity regulates anterior-posterior targeting of olfactory sensory neurons.
We analyzed the agonist-independent GPCR activity for its possible role in receptor-instructed axonal projection. We generated transgenic mice expressing activity mutants of the β2-adrenergic receptor, a well-characterized GPCR with the highest homology to odorant receptors (ORs). We found that muta...
Identification of long-lived proteins reveals exceptional stability of essential cellular structures.
We provide a system-wide identification of proteins with exceptional lifespans in the rat brain. These proteins are inefficiently replenished despite being translated robustly throughout adulthood. Using nucleoporins as a paradigm for long-term protein persistence, we found that nuclear pore complex...
Selection of bone metastasis seeds by mesenchymal signals in the primary tumor stroma.
We show a role of the breast tumor stroma in selecting cancer cells that are primed for metastasis in bone. Cancer-associated fibroblasts (CAFs) in triple-negative (TN) breast tumors skew heterogeneous cancer cell populations toward a predominance of clones that thrive on the CAF-derived factors CXC...
The CRTC1-SIK1 pathway regulates entrainment of the circadian clock.
We have identified a key role for salt inducible kinase 1 (SIK1) and CREB-regulated transcription coactivator 1 (CRTC1) in clock re-setting. An entrainment stimulus causes CRTC1 to coactivate CREB, inducing the expression of Per1 and Sik1. SIK1 then inhibits further shifts of the clock by phosphoryl...