LSD2/KDM1B and Its Cofactor NPAC/GLYR1 Endow a Structural and Molecular Model for Regulation of H3K4 Demethylation

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Highlights? Identifying NPAC as a novel LSD2 cofactor stimulating H3K4 demethylation ? Structure determination of LSD2 alone or in complex with NPAC and histone H3 peptide ? Defining the key NPAC residues essential for its intrinsic LSD2 cofactor activity ? Establishing a molecular model for how a cofactor regulates histone demethylation     

Insights into Negative Regulation by the Glucocorticoid Receptor from Genome-wide Profiling of Inflammatory Cistromes

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Highlights? TLR4 activation dramatically remodels the GR cistrome in macrophages ? Both negative and positive GR enhancers include GREs, NF-κB, and AP-1 sites ? Classical models fail to predict positive or negative polarity of GR regulation ? Hormone treatment marks negative enhancers by histone deacetylation     

Histone Acetylation Regulates Intracellular pH

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Highlights? Global levels of histone acetylation change in response to pH_i alterations ? Histone deacetylation and acetate transport through H⁺-coupled MCTs regulates pH_i ? Proliferation of T cells results in increases in pH_i and global histone acetylation ? HDAC and MCT inhibitors decrease pH_i     

ALKBH5 Is a Mammalian RNA Demethylase that Impacts RNA Metabolism and Mouse Fertility

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Highlights? ALKBH5 is a mammalian m⁶A RNA demethylase ? RNA demethylation affects mRNA export and RNA metabolism ? RNA demethylation is important for mouse fertility ? Reversible mammalian messenger RNA methylation affects gene expression     

A Matrix Protein Silences Transposons and Repeats through Interaction with Retinoblastoma-Associated Proteins

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Highlights? The Arabidopsis matrix protein TEK silences transposons and repeat-containing genes ? Binding of TEK on targets affects chromatin conformation and histone modifications ? TEK protein associates with FVE/MSI5-containing histone deacetylation complex ? TEK directs repressive modification as a key structural component in gene silencing     

Spp1, a Member of the Set1 Complex,Promotes Meiotic DSB Formation in Promoters by Tethering Histone H3K4 Methylation Sites to Chromosome Axes

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Highlights? Spp1 and histone H3K4 residue are important for meiotic DSB formation ? Spp1 physically interacts with the DSB protein Mer2 ? Spp1 in meiosis is not with RNA Pol II, but on chromosome axes in DSB-rich domains ? Spp1’s PHD finger tethers H3K4me3 regions to chromosome axes for DSB formation     

The Mitochondrial RNA-Binding Protein GRSF1 Localizes to RNA Granules and Is Required for Posttranscriptional Mitochondrial Gene Expression

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Highlights? GRSF1 (G-rich sequence binding factor 1) is a mitochondrial RNA-binding protein ? GRSF1 localizes to granules containing newly synthesized RNA in close proximity to mitochondrial nucleoids ? GRSF1 specifically binds one mRNA and two long noncoding RNAs transcribed from contiguous genes on the light strand of mtDNA ? Loss of GRSF1 leads to misloading of RNAs onto the mitochondrial ribosome and a specific translation defect     

Repression of the Long Noncoding RNA-LET by Histone Deacetylase 3 Contributes to Hypoxia-Mediated Metastasis

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Highlights? There is low expression of lncRNA-LET in various tumor tissues ? Hypoxia-induced low expression of lncRNA-LET occurred through histone deacetylase 3 ? The lncRNA-LET is bound to NF90, which increases NF90 degradation by the proteasome ? Low lncRNA-LET expression contributes to hypoxia-induced cell invasion     

Cotranslational Response to Proteotoxic Stress by Elongation Pausing of Ribosomes

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Highlights? Proteotoxic stress reduces global protein synthesis by influencing elongation ? Proteotoxic stress induces ribosome pausing on mRNAs in the first 50 codons ? Molecular chaperones facilitate translation elongation by binding to nascent chains ? Ribosomes fine tune elongation rate in response to proteotoxic stress     

Dissection of DNA Damage Responses Using Multiconditional Genetic Interaction Maps

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Highlights? A resource of genetic modules and networks induced by distinct types of DNA damage ? Networks distinguish DNA damage response pathways with high statistical power ? Rtt109, a histone acetyltransferase, affects the mutagenic bypass of DNA lesions ? The neddylation machinery and Irc21 affect cell-cycle control and genome stability     

Bone marrow-derived cell therapy stimulates endogenous cardiomyocyte progenitors and promotes cardiac repair

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Highlights? c-kit⁺ cell therapy stimulates endogenous cardiomyocyte progenitors ? Nkx2.5- and Gata4-expressing progenitors increase in the infarct border zone ? c-kit⁺ cell therapy leads to improved cardiac function ? No evidence for cardiomyocyte transdifferentiation by bone marrow progenitors     

Structural Basis of Selective Ubiquitination of TRF1 by SCFFbx4

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Highlights? SCF ubiquitin ligase subunit Fbx4 binds TRF1 using an atypical small GTPase fold ? Fbx4 recognizes a globular domain of TRF1, not just short phosphorylated degrons ? Telomere shelterin component TIN2 competes with Fbx4 for TRF1 binding ? TIN2 and SCF^Fbx4 thus control TRF1 ubiquitination and degradation     

The IRP1-HIF-2α Axis Coordinates Iron and Oxygen Sensing with Erythropoiesis and Iron Absorption

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Highlights? Derepression of HIF-2α mRNA in Irp1^?/? mice causes age-dependent polycythemia ? HIF-2α hyperactivity is observed in multiple tissues of Irp1^?/? mice ? The mRNA regulons of IRP1 and IRP2 are separable in vivo ? The IRP1-HIF-2α axis is a therapeutic target for hematologic or oncologic disorders     

Na+ Regulation in the Malaria Parasite Plasmodium falciparum Involves the Cation ATPase PfATP4 and Is a Target of the Spiroindolone Antimalarials

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Highlights? The intraerythrocytic malaria parasite extrudes Na⁺ via a Na⁺-ATPase ? Parasite Na⁺ homeostasis is disrupted by the antimalarial spiroindolones ? Mutations in PfATP4 confer resistance to Na⁺ disruption by the spiroindolones ? PfATP4 is postulated to be a Na⁺ efflux ATPase and a target of the spiroindolones     

The Impact of Aminoglycosides on the Dynamics of Translation Elongation

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Highlights? Combined single-molecule, structural, and biochemical studies on aminoglycoside action ? Aminoglycosides disrupt translation through inhibiting the dynamics of elongation ? Apramycin blocks translocation in translation elongation ? Paromomycin and gentamicin disrupt ribosomal rotation and translocation     

A cis-Acting Element in Retroviral Genomic RNA Links Gag-Pol Ribosomal Frameshifting to Selective Viral RNA Encapsidation

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Highlights? A retroviral RNA packaging element (GRPE) overlaps the Gag-Pol ribosomal frameshift site ? Without two stem loops in GRPE, genomic RNA encapsidation is decreased >50-fold ? Downregulating the translation termination factor eRF1 produces defective virus particles ? GPRE links ribosome frameshifting and effective retroviral packaging     

Deletion of Iron Regulatory Protein 1 Causes Polycythemia and Pulmonary Hypertension in Mice through Translational Derepression of HIF2α

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Highlights? Irp1 deficiency causes polycythemia and pulmonary hypertension ? Irp1 regulates HIF2α translation and expression of EPO and endothelin 1 ? Irp1 represses erythropoiesis to protect tissue iron levels during iron deficiency ? A low-iron diet worsens polycythemia and causes sudden death in Irp1?/? animals     

p58IPK-Mediated Attenuation of the Proapoptotic PERK-CHOP Pathway Allows Malignant Progression upon Low Glucose

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Highlights? Transformation-associated glucose shortage triggers ER stress ? The ER stress acts as barrier to malignancy by triggering UPR-dependent apoptosis ? p58^IPK expression removes the UPR barrier by attenuating its PERK-CHOP branch ? This adaptive mechanism enables implementation of UPR cytoprotective features     

Widespread Regulation of Translation by Elongation Pausing in Heat Shock

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Highlights? Global translation elongation pause at 5′ end of ORFs in severe heat shock ? Modulation of Hsp70 levels/activity affects elongation pausing ? Pausing is associated with hydrophobic N termini ? Hsp70 shows reduced ribosome association and altered interactions in heat stress