Pulmonary surfactant-biomimetic nanoparticles potentiate heterosubtypic influenza immunity

<p>Current influenza vaccines only confer protection against homologous viruses. We synthesized pulmonary surfactant (PS)&ndash;biomimetic liposomes encapsulating 2',3'-cyclic guanosine monophosphate&ndash;adenosine monophosphate (cGAMP), an agonist of the interferon gene inducer STING (stimulator of interferon genes). The adjuvant (PS-GAMP) vigorously augmented influenza vaccine&ndash;induced humoral and CD8<sup>+</sup> T cell immune responses in mice by simulating the early phase of viral infection without concomitant excess inflammation. Two days after intranasal immunization with PS-GAMP&ndash;adjuvanted H1N1 vaccine, strong cross-protection was elicited against distant H1N1 and heterosubtypic H3N2, H5N1, and H7N9 viruses for at least 6 months while maintaining lung-resident memory CD8<sup>+</sup> T cells. Adjuvanticity was then validated in ferrets. When alveolar epithelial cells (AECs) lacked <I>Sting</I> or gap junctions were blocked, PS-GAMP&ndash;mediated adjuvanticity was substantially abrogated in vivo. Thus, AECs play a pivotal role in configuring heterosubtypic immunity.</p>

Vertebrate diapause preserves organisms long term through Polycomb complex members

<p>Diapause is a state of suspended development that helps organisms survive extreme environments. How diapause protects living organisms is largely unknown. Using the African turquoise killifish (<I>Nothobranchius furzeri</I>), we show that diapause preserves complex organisms for extremely long periods of time without trade-offs for subsequent adult growth, fertility, and life span. Transcriptome analyses indicate that diapause is an active state, with dynamic regulation of metabolism and organ development genes. The most up-regulated genes in diapause include Polycomb complex members. The chromatin mark regulated by Polycomb, H3K27me3, is maintained at key developmental genes in diapause, and the Polycomb member CBX7 mediates repression of metabolism and muscle genes in diapause. CBX7 is functionally required for muscle preservation and diapause maintenance. Thus, vertebrate diapause is a state of suspended life that is actively maintained by specific chromatin regulators, and this has implications for long-term organism preservation.</p>

Structure of nucleosome-bound human BAF complex

<p>Mammalian SWI/SNF family chromatin remodelers, BRG1/BRM-associated factor (BAF) and polybromo-associated BAF (PBAF), regulate chromatin structure and transcription, and their mutations are linked to cancers. The 3.7-angstrom-resolution cryo&ndash;electron microscopy structure of human BAF bound to the nucleosome reveals that the nucleosome is sandwiched by the base and the adenosine triphosphatase (ATPase) modules, which are bridged by the actin-related protein (ARP) module. The ATPase motor is positioned proximal to nucleosomal DNA and, upon ATP hydrolysis, engages with and pumps DNA along the nucleosome. The C-terminal &alpha; helix of SMARCB1, enriched in positively charged residues frequently mutated in cancers, mediates interactions with an acidic patch of the nucleosome. AT-rich interactive domain-containing protein 1A (ARID1A) and the SWI/SNF complex subunit SMARCC serve as a structural core and scaffold in the base module organization, respectively. Our study provides structural insights into subunit organization and nucleosome recognition of human BAF complex.</p>

Molecular mechanism of biased signaling in a prototypical G protein-coupled receptor

<p>Biased signaling, in which different ligands that bind to the same G protein&ndash;coupled receptor preferentially trigger distinct signaling pathways, holds great promise for the design of safer and more effective drugs. Its structural mechanism remains unclear, however, hampering efforts to design drugs with desired signaling profiles. Here, we use extensive atomic-level molecular dynamics simulations to determine how arrestin bias and G protein bias arise at the angiotensin II type 1 receptor. The receptor adopts two major signaling conformations, one of which couples almost exclusively to arrestin, whereas the other also couples effectively to a G protein. A long-range allosteric network allows ligands in the extracellular binding pocket to favor either of the two intracellular conformations. Guided by this computationally determined mechanism, we designed ligands with desired signaling profiles.</p>

Angiotensin and biased analogs induce structurally distinct active conformations within a GPCR

<p>Biased agonists of G protein&ndash;coupled receptors (GPCRs) preferentially activate a subset of downstream signaling pathways. In this work, we present crystal structures of angiotensin II type 1 receptor (AT1R) (2.7 to 2.9 angstroms) bound to three ligands with divergent bias profiles: the balanced endogenous agonist angiotensin II (AngII) and two strongly &beta;-arrestin&ndash;biased analogs. Compared with other ligands, AngII promotes more-substantial rearrangements not only at the bottom of the ligand-binding pocket but also in a key polar network in the receptor core, which forms a sodium-binding site in most GPCRs. Divergences from the family consensus in this region, which appears to act as a biased signaling switch, may predispose the AT1R and certain other GPCRs (such as chemokine receptors) to adopt conformations that are capable of activating &beta;-arrestin but not heterotrimeric G<SUB>q</SUB> protein signaling.</p>

Cooling of a levitated nanoparticle to the motional quantum ground state

<p>Quantum control of complex objects in the regime of large size and mass provides opportunities for sensing applications and tests of fundamental physics. The realization of such extreme quantum states of matter remains a major challenge. We demonstrate a quantum interface that combines optical trapping of solids with cavity-mediated light-matter interaction. Precise control over the frequency and position of the trap laser with respect to the optical cavity allowed us to laser-cool an optically trapped nanoparticle into its quantum ground state of motion from room temperature. The particle comprises 10<sup>8</sup> atoms, similar to current Bose-Einstein condensates, with the density of a solid object. Our cooling technique, in combination with optical trap manipulation, may enable otherwise unachievable superposition states involving large masses.</p>

Quantum anomalous Hall effect in intrinsic magnetic topological insulator MnBi2Te4

<p>In a magnetic topological insulator, nontrivial band topology combines with magnetic order to produce exotic states of matter, such as quantum anomalous Hall (QAH) insulators and axion insulators. In this work, we probe quantum transport in MnBi<SUB>2</SUB>Te<SUB>4</SUB> thin flakes&mdash;a topological insulator with intrinsic magnetic order. In this layered van der Waals crystal, the ferromagnetic layers couple antiparallel to each other; atomically thin MnBi<SUB>2</SUB>Te<SUB>4</SUB>, however, becomes ferromagnetic when the sample has an odd number of septuple layers. We observe a zero-field QAH effect in a five&ndash;septuple-layer specimen at 1.4 kelvin, and an external magnetic field further raises the quantization temperature to 6.5 kelvin by aligning all layers ferromagnetically. The results establish MnBi<SUB>2</SUB>Te<SUB>4</SUB> as an ideal arena for further exploring various topological phenomena with a spontaneously broken time-reversal symmetry.</p>

Intrinsic quantized anomalous Hall effect in a moire heterostructure

<p>The quantum anomalous Hall (QAH) effect combines topology and magnetism to produce precisely quantized Hall resistance at zero magnetic field. We report the observation of a QAH effect in twisted bilayer graphene aligned to hexagonal boron nitride. The effect is driven by intrinsic strong interactions, which polarize the electrons into a single spin- and valley-resolved moir&eacute; miniband with Chern number <I>C</I> = 1. In contrast to magnetically doped systems, the measured transport energy gap is larger than the Curie temperature for magnetic ordering, and quantization to within 0.1% of the von Klitzing constant persists to temperatures of several kelvin at zero magnetic field. Electrical currents as small as 1 nanoampere controllably switch the magnetic order between states of opposite polarization, forming an electrically rewritable magnetic memory.</p>

Disassembling 2D van der Waals crystals into macroscopic monolayers and reassembling into artificial lattices

<p>Two-dimensional materials from layered van der Waals (vdW) crystals hold great promise for electronic, optoelectronic, and quantum devices, but technological implementation will be hampered by the lack of high-throughput techniques for exfoliating single-crystal monolayers with sufficient size and high quality. Here, we report a facile method to disassemble vdW single crystals layer by layer into monolayers with near-unity yield and with dimensions limited only by bulk crystal sizes. The macroscopic monolayers are comparable in quality to microscopic monolayers from conventional Scotch tape exfoliation. The monolayers can be assembled into macroscopic artificial structures, including transition metal dichalcogenide multilayers with broken inversion symmetry and substantially enhanced nonlinear optical response. This approach takes us one step closer to mass production of macroscopic monolayers and bulk-like artificial materials with controllable properties.</p>

Old carbon reservoirs were not important in the deglacial methane budget

<p>Permafrost and methane hydrates are large, climate-sensitive old carbon reservoirs that have the potential to emit large quantities of methane, a potent greenhouse gas, as the Earth continues to warm. We present ice core isotopic measurements of methane (<sup>14</sup>C, <sup>13</sup>C, and D) from the last deglaciation, which is a partial analog for modern warming. Our results show that methane emissions from old carbon reservoirs in response to deglacial warming were small (&lt;19 teragrams of methane per year, 95% confidence interval) and argue against similar methane emissions in response to future warming. Our results also indicate that methane emissions from biomass burning in the pre-Industrial Holocene were 22 to 56 teragrams of methane per year (95% confidence interval), which is comparable to today.</p>

Bumble bees display cross-modal object recognition between visual and tactile senses

<p>Many animals can associate object shapes with incentives. However, such behavior is possible without storing images of shapes in memory that are accessible to more than one sensory modality. One way to explore whether there are modality-independent internal representations of object shapes is to investigate cross-modal recognition&mdash;experiencing an object in one sensory modality and later recognizing it in another. We show that bumble bees trained to discriminate two differently shaped objects (cubes and spheres) using only touch (in darkness) or vision (in light, but barred from touching the objects) could subsequently discriminate those same objects using only the other sensory information. Our experiments demonstrate that bumble bees possess the ability to integrate sensory information in a way that requires modality-independent internal representations.</p>

Ancient origins of allosteric activation in a Ser-Thr kinase

<p>A myriad of cellular events are regulated by allostery; therefore, evolution of this process is of fundamental interest. Here, we use ancestral sequence reconstruction to resurrect ancestors of two colocalizing proteins, Aurora A kinase and its allosteric activator TPX2 (targeting protein for Xklp2), to experimentally characterize the evolutionary path of allosteric activation. Autophosphorylation of the activation loop is the most ancient activation mechanism; it is fully developed in the oldest kinase ancestor and has remained stable over 1 billion years of evolution. As the microtubule-associated protein TPX2 appeared, efficient kinase binding to TPX2 evolved, likely owing to increased fitness by virtue of colocalization. Subsequently, TPX2-mediated allosteric kinase regulation gradually evolved. Surprisingly, evolution of this regulation is encoded in the kinase and did not arise by a dominating mechanism of coevolution.</p>

Biocatalytic synthesis of planar chiral macrocycles

<p>Macrocycles can restrict the rotation of substituents through steric repulsions, locking in conformations that provide or enhance the activities of pharmaceuticals, agrochemicals, aroma chemicals, and materials. In many cases, the arrangement of substituents in the macrocycle imparts an element of planar chirality. The difficulty in predicting when planar chirality will arise, as well as the limited number of synthetic methods to impart selectivity, have led to planar chirality being regarded as an irritant. We report a strategy for enantio- and atroposelective biocatalytic synthesis of planar chiral macrocycles. The macrocycles can be formed with high enantioselectivity from simple building blocks and are decorated with functionality that allows one to further modify the macrocycles with diverse structural features.</p>

How mycorrhizal associations drive plant population and community biology

<p>Mycorrhizal fungi provide plants with a range of benefits, including mineral nutrients and protection from stress and pathogens. Here we synthesize current information about how the presence and type of mycorrhizal association affect plant communities. We argue that mycorrhizal fungi regulate seedling establishment and species coexistence through stabilizing and equalizing mechanisms such as soil nutrient partitioning, feedback to soil antagonists, differential mycorrhizal benefits, and nutrient trade. Mycorrhizal fungi have strong effects on plant population and community biology, with mycorrhizal type&ndash;specific effects on seed dispersal, seedling establishment, and soil niche differentiation, as well as interspecific and intraspecific competition and hence plant diversity.</p>

A cell atlas of human thymic development defines T cell repertoire formation

<p>The thymus provides a nurturing environment for the differentiation and selection of T cells, a process orchestrated by their interaction with multiple thymic cell types. We used single-cell RNA sequencing to create a cell census of the human thymus across the life span and to reconstruct T cell differentiation trajectories and T cell receptor (TCR) recombination kinetics. Using this approach, we identified and located in situ CD8&alpha;&alpha;<sup>+</sup> T cell populations, thymic fibroblast subtypes, and activated dendritic cell states. In addition, we reveal a bias in TCR recombination and selection, which is attributed to genomic position and the kinetics of lineage commitment. Taken together, our data provide a comprehensive atlas of the human thymus across the life span with new insights into human T cell development.</p>

Genome-wide identification of interferon-sensitive mutations enables influenza vaccine design

<p>In conventional attenuated viral vaccines, immunogenicity is often suboptimal. Here we present a systematic approach for vaccine development that eliminates interferon (IFN)&ndash;modulating functions genome-wide while maintaining virus replication fitness. We applied a quantitative high-throughput genomics system to influenza A virus that simultaneously measured the replication fitness and IFN sensitivity of mutations across the entire genome. By incorporating eight IFN-sensitive mutations, we generated a hyper&ndash;interferon-sensitive (HIS) virus as a vaccine candidate. HIS virus is highly attenuated in IFN-competent hosts but able to induce transient IFN responses, elicits robust humoral and cellular immune responses, and provides protection against homologous and heterologous viral challenges. Our approach, which attenuates the virus and promotes immune responses concurrently, is broadly applicable for vaccine development against other pathogens.</p>

A self-assembled nanoscale robotic arm controlled by electric fields

<p>The use of dynamic, self-assembled DNA nanostructures in the context of nanorobotics requires fast and reliable actuation mechanisms. We therefore created a 55-nanometer&ndash;by&ndash;55-nanometer DNA-based molecular platform with an integrated robotic arm of length 25 nanometers, which can be extended to more than 400 nanometers and actuated with externally applied electrical fields. Precise, computer-controlled switching of the arm between arbitrary positions on the platform can be achieved within milliseconds, as demonstrated with single-pair Fo&#x0308;rster resonance energy transfer experiments and fluorescence microscopy. The arm can be used for electrically driven transport of molecules or nanoparticles over tens of nanometers, which is useful for the control of photonic and plasmonic processes. Application of piconewton forces by the robot arm is demonstrated in force-induced DNA duplex melting experiments.</p>

Quantum liquid droplets in a mixture of Bose-Einstein condensates

<p>Quantum droplets are small clusters of atoms self-bound by the balance of attractive and repulsive forces. Here, we report on the observation of droplets solely stabilized by contact interactions in a mixture of two Bose-Einstein condensates. We demonstrate that they are several orders of magnitude more dilute than liquid helium by directly measuring their size and density via in situ imaging. We show that the droplets are stablized against collapse by quantum fluctuations and that they require a minimum atom number to be stable. Below that number, quantum pressure drives a liquid-to-gas transition that we map out as a function of interaction strength. These ultradilute isotropic liquids remain weakly interacting and constitute an ideal platform to benchmark quantum many-body theories.</p>

Hydraulic fracturing volume is associated with induced earthquake productivity in the Duvernay play

<p>A sharp increase in the frequency of earthquakes near Fox Creek, Alberta, began in December 2013 in response to hydraulic fracturing. Using a hydraulic fracturing database, we explore relationships between injection parameters and seismicity response. We show that induced earthquakes are associated with completions that used larger injection volumes (10<sup>4</sup> to 10<sup>5</sup> cubic meters) and that seismic productivity scales linearly with injection volume. Injection pressure and rate have an insignificant association with seismic response. Further findings suggest that geological factors play a prominent role in seismic productivity, as evidenced by spatial correlations. Together, volume and geological factors account for ~96% of the variability in the induced earthquake rate near Fox Creek. This result is quantified by a seismogenic index&ndash;modified frequency-magnitude distribution, providing a framework to forecast induced seismicity.</p>

Chiromagnetic nanoparticles and gels

<p>Chiral inorganic nanostructures have high circular dichroism, but real-time control of their optical activity has so far been achieved only by irreversible chemical changes. Field modulation is a far more desirable path to chiroptical devices. We hypothesized that magnetic field modulation can be attained for chiral nanostructures with large contributions of the magnetic transition dipole moments to polarization rotation. We found that dispersions and gels of paramagnetic Co<SUB>3</SUB>O<SUB>4</SUB> nanoparticles with chiral distortions of the crystal lattices exhibited chiroptical activity in the visible range that was 10 times as strong as that of nonparamagnetic nanoparticles of comparable size. Transparency of the nanoparticle gels to circularly polarized light beams in the ultraviolet range was reversibly modulated by magnetic fields. These phenomena were also observed for other nanoscale metal oxides with lattice distortions from imprinted amino acids and other chiral ligands. The large family of chiral ceramic nanostructures and gels can be pivotal for new technologies and knowledge at the nexus of chirality and magnetism.</p>

Digitization of multistep organic synthesis in reactionware for on-demand pharmaceuticals

<p>Chemical manufacturing is often done at large facilities that require a sizable capital investment and then produce key compounds for a finite period. We present an approach to the manufacturing of fine chemicals and pharmaceuticals in a self-contained plastic reactionware device. The device was designed and constructed by using a chemical to computer-automated design (ChemCAD) approach that enables the translation of traditional bench-scale synthesis into a platform-independent digital code. This in turn guides production of a three-dimensional printed device that encloses the entire synthetic route internally via simple operations. We demonstrate the approach for the -aminobutyric acid receptor agonist, (&plusmn;)-baclofen, establishing a concept that paves the way for the local manufacture of drugs outside of specialist facilities.</p>

A global atlas of the dominant bacteria found in soil

<p>The immense diversity of soil bacterial communities has stymied efforts to characterize individual taxa and document their global distributions. We analyzed soils from 237 locations across six continents and found that only 2% of bacterial phylotypes (~500 phylotypes) consistently accounted for almost half of the soil bacterial communities worldwide. Despite the overwhelming diversity of bacterial communities, relatively few bacterial taxa are abundant in soils globally. We clustered these dominant taxa into ecological groups to build the first global atlas of soil bacterial taxa. Our study narrows down the immense number of bacterial taxa to a "most wanted" list that will be fruitful targets for genomic and cultivation-based efforts aimed at improving our understanding of soil microbes and their contributions to ecosystem functioning.</p>

Improving refugee integration through data-driven algorithmic assignment

<p>Developed democracies are settling an increased number of refugees, many of whom face challenges integrating into host societies. We developed a flexible data-driven algorithm that assigns refugees across resettlement locations to improve integration outcomes. The algorithm uses a combination of supervised machine learning and optimal matching to discover and leverage synergies between refugee characteristics and resettlement sites. The algorithm was tested on historical registry data from two countries with different assignment regimes and refugee populations, the United States and Switzerland. Our approach led to gains of roughly 40 to 70%, on average, in refugees&rsquo; employment outcomes relative to current assignment practices. This approach can provide governments with a practical and cost-efficient policy tool that can be immediately implemented within existing institutional structures.</p>

Dicer uses distinct modules for recognizing dsRNA termini

<p>Invertebrates rely on Dicer to cleave viral double-stranded RNA (dsRNA), and <I>Drosophila</I> Dicer-2 distinguishes dsRNA substrates by their termini. Blunt termini promote processive cleavage, while 3' overhanging termini are cleaved distributively. To understand this discrimination, we used cryo&ndash;electron microscopy to solve structures of <I>Drosophila</I> Dicer-2 alone and in complex with blunt dsRNA. Whereas the Platform-PAZ domains have been considered the only Dicer domains that bind dsRNA termini, unexpectedly, we found that the helicase domain is required for binding blunt, but not 3' overhanging, termini. We further showed that blunt dsRNA is locally unwound and threaded through the helicase domain in an adenosine triphosphate&ndash;dependent manner. Our studies reveal a previously unrecognized mechanism for optimizing antiviral defense and set the stage for the discovery of helicase-dependent functions in other Dicers.</p>

Phosphoethanolamine cellulose: A naturally produced chemically modified cellulose

<p>Cellulose is a major contributor to the chemical and mechanical properties of plants and assumes structural roles in bacterial communities termed biofilms. We find that <I>Escherichia coli</I> produces chemically modified cellulose that is required for extracellular matrix assembly and biofilm architecture. Solid-state nuclear magnetic resonance spectroscopy of the intact and insoluble material elucidates the zwitterionic phosphoethanolamine modification that had evaded detection by conventional methods. Installation of the phosphoethanolamine group requires BcsG, a proposed phosphoethanolamine transferase, with biofilm-promoting cyclic diguanylate monophosphate input through a BcsE-BcsF-BcsG transmembrane signaling pathway. The <I>bcsEFG</I> operon is present in many bacteria, including <I>Salmonella</I> species, that also produce the modified cellulose. The discovery of phosphoethanolamine cellulose and the genetic and molecular basis for its production offers opportunities to modulate its production in bacteria and inspires efforts to biosynthetically engineer alternatively modified cellulosic materials.</p>

Structural mechanisms of centromeric nucleosome recognition by the kinetochore protein CENP-N

<p>Accurate chromosome segregation requires the proper assembly of kinetochore proteins. A key step in this process is the recognition of the histone H3 variant CENP-A in the centromeric nucleosome by the kinetochore protein CENP-N. We report cryo&ndash;electron microscopy (cryo-EM), biophysical, biochemical, and cell biological studies of the interaction between the CENP-A nucleosome and CENP-N. We show that human CENP-N confers binding specificity through interactions with the L1 loop of CENP-A, stabilized by electrostatic interactions with the nucleosomal DNA. Mutational analyses demonstrate analogous interactions in <I>Xenopus</I>, which are further supported by residue-swapping experiments involving the L1 loop of CENP-A. Our results are consistent with the coevolution of CENP-N and CENP-A and establish the structural basis for recognition of the CENP-A nucleosome to enable kinetochore assembly and centromeric chromatin organization.</p>

Multiplexed gene synthesis in emulsions for exploring protein functional landscapes

<p>Improving our ability to construct and functionally characterize DNA sequences would broadly accelerate progress in biology. Here, we introduce DropSynth, a scalable, low-cost method to build thousands of defined gene-length constructs in a pooled (multiplexed) manner. DropSynth uses a library of barcoded beads that pull down the oligonucleotides necessary for a gene&rsquo;s assembly, which are then processed and assembled in water-in-oil emulsions. We used DropSynth to successfully build more than 7000 synthetic genes that encode phylogenetically diverse homologs of two essential genes in <I>Escherichia coli</I>. We tested the ability of phosphopantetheine adenylyltransferase homologs to complement a knockout <I>E. coli</I> strain in multiplex, revealing core functional motifs and reasons underlying homolog incompatibility. DropSynth coupled with multiplexed functional assays allows us to rationally explore sequence-function relationships at an unprecedented scale.</p>

Toward dynamic structural biology: Two decades of single-molecule Fo&#x0308;rster resonance energy transfer

<p>Classical structural biology can only provide static snapshots of biomacromolecules. Single-molecule Fo&#x0308;rster resonance energy transfer (smFRET) paved the way for studying dynamics in macromolecular structures under biologically relevant conditions. Since its first implementation in 1996, smFRET experiments have confirmed previously hypothesized mechanisms and provided new insights into many fundamental biological processes, such as DNA maintenance and repair, transcription, translation, and membrane transport. We review 22 years of contributions of smFRET to our understanding of basic mechanisms in biochemistry, molecular biology, and structural biology. Additionally, building on current state-of-the-art implementations of smFRET, we highlight possible future directions for smFRET in applications such as biosensing, high-throughput screening, and molecular diagnostics.</p>

Membrane protein insertion through a mitochondrial {beta}-barrel gate

<p>The biogenesis of mitochondria, chloroplasts, and Gram-negative bacteria requires the insertion of &beta;-barrel proteins into the outer membranes. Homologous Omp85 proteins are essential for membrane insertion of &beta;-barrel precursors. It is unknown if precursors are threaded through the Omp85-channel interior and exit laterally or if they are translocated into the membrane at the Omp85-lipid interface. We have mapped the interaction of a precursor in transit with the mitochondrial Omp85-channel Sam50 in the native membrane environment. The precursor is translocated into the channel interior, interacts with an internal loop, and inserts into the lateral gate by &beta;-signal exchange. Transport through the Omp85-channel interior followed by release through the lateral gate into the lipid phase may represent a basic mechanism for membrane insertion of &beta;-barrel proteins.</p>

The epigenetic control of stemness in CD8+ T cell fate commitment

<p>After priming, nai&#x0308;ve CD8<sup>+</sup> T lymphocytes establish specific heritable transcription programs that define progression to long-lasting memory cells or to short-lived effector cells. Although lineage specification is critical for protection, it remains unclear how chromatin dynamics contributes to the control of gene expression programs. We explored the role of gene silencing by the histone methyltransferase Suv39h1. In murine CD8<sup>+</sup> T cells activated after <I>Listeria monocytogenes</I> infection, Suv39h1-dependent trimethylation of histone H3 lysine 9 controls the expression of a set of stem cell&ndash;related memory genes. Single-cell RNA sequencing revealed a defect in silencing of stem/memory genes selectively in <I>Suv39h1</I>-defective T cell effectors. As a result, <I>Suv39h1</I>-defective CD8<sup>+</sup> T cells show sustained survival and increased long-term memory reprogramming capacity. Thus, Suv39h1 plays a critical role in marking chromatin to silence stem/memory genes during CD8<sup>+</sup> T effector terminal differentiation.</p>