Latent Enhancers Activated by Stimulation in Differentiated Cells

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Highlights? Latent enhancers are regulatory elements unmarked and unbound in differentiated cells ? Stimulus-dependent TFs co-opt lineage-determining TFs to activate latent enhancers ? Latent enhancers may confer short-term memory of environmental exposure ? Environmental stimulation qualitatively alters the pre-existing enhancer repertoire     

Olig2 Targets Chromatin Remodelers to Enhancers to Initiate Oligodendrocyte Differentiation

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Highlights? Activation of the Brg1 chromatin-remodeling complex drives OPC differentiation ? Olig2 prepatterns and directs Brg1 targeting to oligodendrocyte-specific enhancers ? Functional and stage-dependent Olig2/Brg1 targeting in oligodendrocyte development ? Olig2/Brg1 targeting coupled with epigenetic marking defines oligodendrocyte identity     

The RNA Pol II Elongation Factor Ell3 Marks Enhancers in ES Cells and Primes Future Gene Activation

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Highlights? Ell3 is preferentially found at active, poised, and inactive enhancers in ES cells ? Promoter-proximal Pol II occupancy at key developmental genes requires Ell3 ? Cohesin functions in Ell3-associated enhancer-promoter communication ? Recruitment of P-TEFb within SEC during differentiation is Ell3 dependent     

DAD2 Is an α/β Hydrolase Likely to Be Involved in the Perception of the Plant Branching Hormone,Strigolactone

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Highlights? DAD2 gene, identified by transposon tagging, encodes an α/β hydrolase fold protein ? DAD2 acts in the shoot; mutants are insensitive to strigolactones ? DAD2 crystal structure shows an internal cavity capable of binding strigolactones ? DAD2 can hydrolyze the strigolactone GR24     

YihE Kinase Is a Central Regulator of Programmed Cell Death in Bacteria

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Highlights? YihE protein kinase is a central regulator of programmed cell death in bacteria ? YihE antagonizes the MazEF toxin-antitoxin module to suppress stress-mediated death ? YihE links MazF, Cpx, and a cascade of ROS into a unified stress-response scheme ? YihE is a potential target of small-molecule enhancers of antimicrobial lethality     

HSF-1 regulators DDL-1/2 link insulin-like signaling to heat-shock responses and modulation of longevity

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Highlights? C. elegans DAF-2 insulin-like signaling negatively regulates HSF-1 activity ? DDL-1 and DDL-2 are negative regulators of HSF-1 ? Formation of a complex containing DDL-1/2 and HSF-1 inhibits HSF-1 activity ? DAF-2 signaling promotes DHIC formation by inhibiting DDL-1 phosphorylation     

Sunitinib Does Not Accelerate Tumor Growth in Patients with Metastatic Renal Cell Carcinoma

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Highlights? Drugs targeting the tumor vasculature are under investigation for cancer treatment ? However, changes in tumor vasculature may promote tumor growth and/or tumor spread ? Our analysis shows that sunitinib does not accelerate tumor growth in humans ? Sunitinib administration has positive effects and no negative effects when stopped     

Adaptor protein self-assembly drives the control of a cullin-RING ubiquitin ligase

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Highlights? The crystal structure of the heterotetrameric CRL3-SPOP ubiquitin ligase is reported ? Substrate adaptor proteins are recruited to CRL complexes through a signature motif ? Tandem BTB and BACK domains potentiate assembly and activity of the CRL3-SPOP ligase ? The SPOPL negative regulator creates a molecular rheostat to fine-tune CRL3 activity     

SIP1 Mediates Cell-Fate Decisions between Neuroectoderm and Mesendoderm in Human Pluripotent Stem Cells

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Highlights? Smad-interacting protein 1 (SIP1) regulates hESC differentiation ? SIP1 upregulation promotes neuroectodermal differentiation ? SIP1 inhibits mesendodermal and endodermal differentiation ? SMAD2/3 and NANOG/OCT4/SOX2 cooperatively regulate SIP1 expression     

Keeping cell identity in Arabidopsis requires PRC1 RING-finger homologs that catalyze H2A monoubiquitination

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Highlights? AtBMI1A/B proteins prevent misexpression of embryonic traits in somatic cells ? PRC2 and AtBMI1A/B proteins maintain cells in their differentiated state ? AtBMI1A/B proteins mediate H2A monoubiquitination     

Perivascular Nitric Oxide Activates Notch Signaling and Promotes Stem-like Character in PDGF-Induced Glioma Cells

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Highlights? Perivascular niche nitric oxide activates Notch in PDGF-induced gliomas ? Notch signaling drives tumor stem-like characteristics and reduces survival ? Loss of eNOS activity decreases tumor stem-like characteristics ? Suppressing eNOS activity prolongs survival in glioma-bearing mice     

Comprehensive Analysis of Silencing Mutants Reveals Complex Regulation of the Arabidopsis Methylome

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Highlights? Genome-wide single-nucleotide resolution methylation maps in 86 silencing mutants ? Complex interplays between different DNA methylation pathways ? Identification of novel regulators of DNA methylation     

Protein model discrimination using mutational sensitivity derived from deep sequencing

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Highlights? Individual mutant phenotypes in a saturation library derived via deep sequencing ? Residue depth and active-site residue derivation from mutant phenotypes ? Mutant-phenotype-derived parameters used for protein model discrimination ? Derivation of sequence-structure-function relationships without protein isolation     

The Centrosome Regulates the Rab11- Dependent Recycling Endosome Pathway at Appendages of the Mother Centriole

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Highlights? Endosome-proteins localize to centrosomes independent of membranes ? Rab11 and its modulators localize to mother centriole appendages ? Mother centriole appendages regulate membrane recycling through Rab11     

Visualizing the Determinants of Viral RNA Recognition by Innate Immune Sensor RIG-I

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Highlights? Crystallographic structure of RIG-I with 5′ triphosphorylated RNA duplex and ADP ? Solution biophysical analysis of ATP-dependent RIG-I conformational change ? The structural basis for ATP-stimulated RIG-I activation     

Sculpting of DNA at Abasic Sites by DNA Glycosylase Homolog Mag2

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Highlights? Unflipped AP site stabilized by helix-hairpin-helix DNA glycosylase homolog Mag2 ? Nonenzymatic AP site recognition and DNA sculpting ? Sculpting of DNA conformation enhances substrate transfer between proteins     

Two Deubiquitylases Act on Mitofusin and Regulate Mitochondrial Fusion along Independent Pathways

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Highlights? Mitochondrial fusion is regulated by independent ubiquitylation pathways ? The deubiquitylase Ubp2 promotes fusion, whereas Ubp12 inhibits fusion events ? Self-assembly and ubiquitylation cooperatively enable mitochondrial fusion ? Yeast mitofusin is sequentially ubiquitylated     

Spatial Restriction of FGF Signaling by a Matrix Metalloprotease Controls Branching Morphogenesis

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Highlights? Drosophila Matrix Metalloprotease (Mmp) inhibits FGF signaling ? An FGF – MMP feedback loop regulates branching morphogenesis ? Mmp2 spatially regulates FGF signaling in epithelia     

Solution Conformations of Prototype Foamy Virus Integrase and Its Stable Synaptic Complex with U5 Viral DNA

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Highlights? Missing domains in PFV intasome revealed by SAXS/SANS ? PFV IN undergoes dramatic changes in conformation and oligomerization upon binding DNA ? Strand transfer inhibitors do not alter quaternary structure of PFV intasome