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     

Plasma Membrane Tethering of the Cortical ER Necessitates Its Finely Reticulated Architecture

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Highlights? The VAP proteins sustain the ER-plasma membrane attachment in fission yeast ? Footprint of the ER on the cortex is functionally insulated from the cytosol ? Division-site placement requires a patchwork of cortical sites accessible to cytosol     

Sirt3 promotes the urea cycle and fatty acid oxidation during dietary restriction

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Highlights? High-throughput analyses identify potential targets of Sirt3 ? Sirt3 deacetylates and stimulates ornithine transcarbamoylase ? Caloric restriction induces Sirt3 expression and stimulation of the urea cycle ? Sirt3 regulates amino acid catabolism and β-oxidation during caloric restriction     

Regeneration of Human Tumor Antigen-Specific T Cells from iPSCs Derived from Mature CD8+ T Cells

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Highlights? iPSCs generated from T cells specific for the MART-1 melanoma epitope ? Differentiation of iPSCs into T cells with a MART-1 specific T cell receptor ? MART-1-based stimulation of T cells demonstrates retained antigen specificity     

Near-Real-Time Feature-Selective Modulations in Human Cortex

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Highlights? Understanding cognition requires knowledge of temporal dynamics of neural behavior ? SSVEP may be used to reconstruct orientation response profiles at a subsecond scale ? Provides a metric that can rapidly track information processing in human cortex     

Multiple Epigenetic Modifiers Induce Aggressive Viral Extinction in Extraembryonic Endoderm Stem Cells

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Highlights? Mouse ESCs, TSCs, and XEN cells have different capacities to suppress retroviral activity ? RNAi screens identified epigenetic factors that mediate silencing of retroviruses ? Candidates modulate integrated, as well as endogenous, retroviral element silencing ? An Argonaute protein binds integrated provirus and may mediate retroviral extinction     

Structures of adnectin/protein complexes reveal an expanded binding footprint

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Highlights? Adnectins interact with targets using multiple binding modes ? Residues outside of the diversified loops can interact with ligand ? Some fixed scaffold residues contribute to the binding energy ? Adnectins can interact with epitopes that may be inaccessible to antibodies     

Early Folding Events Protect Aggregation-Prone Regions of a β-Rich Protein

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Highlights? The folding pathway of a β-barrel protein protects it from aggregation ? The rate-determining transition state of CRABP1 is polarized and malleable ? Regions constituting the aggregate core of CRABP1 are protected early in folding ? Early barrel closure in iLBPs may offer a general strategy for productive folding     

Information encoded in non-native States drives substrate-chaperone pairing

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Highlights? In vitro refolding intermediates are aptly targeted to specific chaperones ? Substrate-chaperone pairing depends on their relative affinity ? Structure of the intermediates play crucial role in precise chaperone targeting ? Substrates may be mistargeted due to large alterations in chaperone molar ratios     

Leukemia Fusion Target AF9 Is an Intrinsically Disordered Transcriptional Regulator that Recruits Multiple Partners via Coupled Folding and Binding

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Highlights? The AF9 AHD is intrinsically disordered ? The AHD recruits AF4, BCoR, Dot1L, and hPC3 by coupled folding and binding ? AF9 binding partners compete for binding to a common site ? Dynamics of the AF4-AF9 complex may facilitate exchange between partners     

A three-state model of telomere control over human proliferative boundaries

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Highlights? Human telomeres are protected from the DDR by a higher-order structure. ? Intermediate-state telomeres are susceptible to a DDR and regulate senescence. ? Uncapped-state telomeres are susceptible to fusions and induce crisis. ? Intermediate-state telomeres regulate the prolonged mitosis checkpoint. ? Telomeres may serve as epigenetic sensors of cellular stress.     

Out but Not In: The Large Transmembrane β-Barrel Protein FhuA Unfolds but Cannot Refold via β-Hairpins

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Highlights? Mechanical un- and refolding studies of single large transmembrane β-barrel proteins ? FhuA unfolds via highly reproducible steps formed by single β-hairpins ? Once unfolded, FhuA folds into highly irreproducible structures ? To assist folding into the membrane, FhuA may require cofactors     

Calponin 2 Acts As an Effector of Noncanonical Wnt-Mediated Cell Polarization during Neural Crest Cell Migration

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Highlights? Cnn2 is expressed in NCCs and required for their migration in frogs and chicks ? Cnn2 is inactivated by noncanonical Wnt signaling ? Loss of Cnn2 causes a switch from cortical actin to central stress fibers ? Cnn2 polarizes the actin cytoskeleton downstream of PCP     

Human TFIID Binds to Core Promoter DNA in a Reorganized Structural State

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Highlights? TFIID has distinct conformations with different positions of the TBP-containing lobe ? A rearranged state of TFIID interacts with promoter DNA in a TFIIA-dependent manner ? TFIID induces multiple topological changes on promoter DNA around the start site ? The different conformations of TFIID may serve as targets for regulatory factors     

Lactocepin secreted by Lactobacillus exerts anti-inflammatory effects by selectively degrading proinflammatory chemokines

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Highlights? PrtP-encoded lactocepin degrades proinflammatory chemokines, notably IP-10 ? Lactocepin reduces lymphocyte infiltration in an ileitis model ? Lactocepin lowers IP-10 levels and cecal inflammation in a colitis model ? Lactocepin-based therapy may be a treatment option for chemokine-mediated diseases     

Supernumerary centrosomes nucleate extra cilia and compromise primary cilium signaling

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Highlights? Supernumerary centrosomes nucleate cilia, resulting in superciliated cells (SCC) ? Ciliary proteins are reduced in concentration in SCC, compromising signaling ? Presence of extra cilia disrupts epithelial organization in 3D spheroid culture ? Extra cilia may contribute to disease phenotypes by disrupting signaling     

Tmem64 Modulates Calcium Signaling during RANKL-Mediated Osteoclast Differentiation

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Highlights? Tmem64-deficient mice show increased bone volume ? Tmem64 deficiency reduces [Ca²⁺]_i oscillation in response to RANKL stimulation ? Tmem64 interacts with SERCA2 ? Tmem64 positively regulates osteoclast formation via SERCA2/Ca²⁺ signaling     

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     

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