Calorie Restriction and SIRT3 Trigger Global Reprogramming of the Mitochondrial Protein Acetylome

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Highlights? MS quantifies 1,578 mitochondrial acetyl sites altered during CR and loss of SIRT3 ? SIRT3 functions as a prominent regulator in CR adaptation ? CR and SIRT3 regulate previously unrecognized processes in mitochondria ? We provide an acetylation atlas for understanding mitochondrial regulation in CR     

Sustained PU.1 Levels Balance Cell-Cycle Regulators to Prevent Exhaustion of Adult Hematopoietic Stem Cells

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Highlights? PU.1 prevents hematopoietic stem cell (HSC) exhaustion ? PU.1 is a master regulator of cell-cycle genes in HSCs ? PU.1 binding mediates chromosome looping in HSCs ? Positive autoregulation via a ?14 kb enhancer sustains PU.1 levels in HSCs     

Metabolic Regulation by the Mitochondrial Phosphatase PTPMT1 Is Required for Hematopoietic Stem Cell Differentiation

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Highlights? PTPMT1 depletion causes cell cycle delay and differentiation block in HSCs ? The HSC pool in PTPMT1 knockout mice is drastically (～40-fold) expanded ? Mitochondrial metabolism is altered and AMPK is highly activated in knockout HSCs ? PTPMT1 PIP substrates directly enhance fatty-acid-induced activation of UCP2     

Cdc42 activity regulates hematopoietic stem cell aging and rejuvenation

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Highlights? Constitutively increasing Cdc42 activity causes aging of young HSCs ? Elevated Cdc42 activity correlates with a loss of cell polarity in aged HSCs ? Inhibition of Cdc42 activity rejuvenates aged LT-HSC function ? Cdc42 inhibition restores the level and spatial distribution of AcH4K16     

Endothelial Cells Are Essential for the Self-Renewal and Repopulation of Notch-Dependent Hematopoietic Stem Cells

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Highlights? Coculture with endothelial cells promotes HSC expansion and self-renewal ? Endothelial cell effect on HSCs mediated by Notch signaling ? In vivo, sinusoidal endothelial cells (SECs) express Notch ligands ? Blocking vessel remodeling impairs hematopoietic recovery after irradiation     

Deubiquitination of NLRP3 by BRCC3 Critically Regulates Inflammasome Activity

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Highlights? Inhibition of deubiquitination blocks inflammasome activation ? Inhibition of deubiquitination induces NLRP3 polyubiquitination ? Deubiquitination of NLRP3 regulates the activation of inflammasome ? The deubiquitinating enzyme BRCC3 deubiquitinates the LRR domain of NLRP3     

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     

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     

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     

β1 Integrin Establishes Endothelial Cell Polarity and Arteriolar Lumen Formation via a Par3-Dependent Mechanism

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Highlights? β1 integrin deletion results in loss of endothelial polarity and vessel patency ? β1 integrin regulates cell-cell adhesion protein distribution in the endothelium ? Polarity loss is typified by decreased Par3 expression ? Par3 can partially rescue lumen formation in the β1 integrin mutant     

Proliferation-Dependent Alterations of the DNA Methylation Landscape Underlie Hematopoietic Stem Cell Aging

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Highlights? Locus-specific alterations of the DNA methylome accompany HSC aging ? Methylation changes target genes expressed downstream of HSCs to alter HSC potential ? HSC potential, DNA methylation, and replicative limits depend on divisional history ? Aging and forced proliferation of HSC results in DNA hypermethylation of PRC2 targets     

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     

The Retroviral Restriction Ability of SAMHD1, but Not Its Deoxynucleotide Triphosphohydrolase Activity,Is Regulated by Phosphorylation

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Highlights? SAMHD1 only exhibits antiviral activity when expressed in noncycling cells ? SAMHD1 is unphosphorylated in noncycling cells ? Reverse genetics revealed that phosphorylated SAMHD1 is repressive for restriction ? SAMHD1 phosphorylation regulates restriction, but not the cellular levels of dNTPs     

MTR1 encodes a secretory fasciclin glycoprotein required for male reproductive development in rice

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Highlights? The fasciclin glycoprotein MTR1 regulates male reproductive development in rice ? Rice male reproductive cells secrete MTR1 to control somatic tapetum development     

Pou5f1-Dependent EGF Expression Controls E-Cadherin Endocytosis,Cell Adhesion,and Zebrafish Epiboly Movements

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Highlights? Pou5f1 regulates EGF expression during oogenesis ? EGFR signaling controls E-cadherin trafficking at blastula and gastrula stages ? E-cadherin subcellular trafficking controls adhesion and cell migration ? Dynamics of E-cadherin adhesion is essential for effective cell migration     

Towards a structural understanding of PARP1 activation and related signalling ADP-ribosyl-transferases

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Highlights? PARP1 recognizes DNA strand breaks through substrate-assisted dimerization. ? PARP1 ZFIII and WGR domains link DNA break recognition to enzyme activation. ? Tankyrase-dependent PARylation regulates Wnt signalling and Cherubism syndrome.     

The MRN-CtIP Pathway Is Required for Metaphase Chromosome Alignment

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Highlights? The MRN-CtIP pathway is required for metaphase chromosome alignment in egg extracts ? MRN inhibition interferes with spindle assembly around DNA-coated beads ? MRN inhibition in cells causes a metaphase delay and disrupts the RanGTP gradient ? The MRN complex regulates the stable association of RCC1 to chromatin