Loss of net neutrality could harm research p.147

doi: 10.1038/d41586-017-07842-0

Bureaucratic drag dents Japan’s nuclear science p.147

doi: 10.1038/d41586-017-08464-2

How to avoid glib interdisciplinarity p.148

doi: 10.1038/d41586-017-08465-1

Nine researchers sue University of Rochester over sexual-harassment allegations p.155

doi: 10.1038/d41586-017-08235-z

Tasmanian tiger genome offers clues to its extinction p.156

doi: 10.1038/d41586-017-08368-1

Acupuncture in cancer study reignites debate about controversial technique p.157

doi: 10.1038/d41586-017-08309-y

US graduate students in uproar over proposed tax hike p.157

doi: 10.1038/d41586-017-07879-1

Argentinian geoscientist faces criminal charges over glacier survey p.158

doi: 10.1038/d41586-017-08236-y

The science that’s never been cited p.162

doi: 10.1038/d41586-017-08404-0

Early embryos kept in check p.178

doi: 10.1038/d41586-017-07436-w

Stellar cannibalism in fits and starts p.179

doi: 10.1038/d41586-017-08286-2

A dark side to omega-3 fatty acids p.180

doi: 10.1038/d41586-017-07678-8

Longer life through an odd Pol enzyme p.182

doi: 10.1038/d41586-017-07435-x

Antarctic ice dynamics in warm climates p.183

doi: 10.1038/d41586-017-08285-3

Viruses hijack a long non-coding RNA p.184

doi: 10.1038/d41586-017-07692-w

Enhancing mitochondrial proteostasis reduces amyloid-β proteotoxicity p.187

doi: 10.1038/nature25143

Alcohol-abuse drug disulfiram targets cancer via p97 segregase adaptor NPL4 p.194

doi: 10.1038/nature25016

Electron cryo-microscopy structure of a human TRPM4 channel p.200

doi: 10.1038/nature24674

Structures of the calcium-activated, non-selective cation channel TRPM4 p.205

doi: 10.1038/nature24997

Magnetically gated accretion in an accreting ‘non-magnetic’ white dwarf p.210

doi: 10.1038/nature24653

An electric-eel-inspired soft power source from stacked hydrogels p.214

doi: 10.1038/nature24670

Force loading explains spatial sensing of ligands by cells p.219

doi: 10.1038/nature24662

Initiation and long-term instability of the East Antarctic Ice Sheet p.225

doi: 10.1038/nature25026

Large emissions from floodplain trees close the Amazon methane budget p.230

doi: 10.1038/nature24639

A compositional tipping point governing the mobilization and eruption style of rhyolitic magma p.235

doi: 10.1038/nature24488

Pluripotent state transitions coordinate morphogenesis in mouse and human embryos p.239

doi: 10.1038/nature24675

Moving beyond microbiome-wide associations to causal microbe identification p.244

doi: 10.1038/nature25019

Inhibition of soluble epoxide hydrolase prevents diabetic retinopathy p.248

doi: 10.1038/nature25013

Runx3 programs CD8+ T cell residency in non-lymphoid tissues and tumours p.253

Tissue-resident memory CD8+ T (T_RM) cells are found at common sites of pathogen exposure, where they elicit rapid and robust protective immune responses. However, the molecular signals that control T_RM cell differentiation and homeostasis are not fully understood. Here we show that mouse T_RM precursor cells represent a unique CD8+ T cell subset that is distinct from the precursors of circulating memory cell populations at the levels of gene expression and chromatin accessibility. Using computational and pooled in vivo RNA interference screens, we identify the transcription factor Runx3 as a key regulator of T_RM cell differentiation and homeostasis. Runx3 was required to establish T_RM cell populations in diverse tissue environments, and supported the expression of crucial tissue-residency genes while suppressing genes associated with tissue egress and recirculation. Furthermore, we show that human and mouse tumour-infiltrating lymphocytes share a core tissue-residency gene-expression signature with T_RM cells that is associated with Runx3 activity. In a mouse model of adoptive T cell therapy for melanoma, Runx3-deficient CD8+ tumour-infiltrating lymphocytes failed to accumulate in tumours, resulting in greater rates of tumour growth and mortality. Conversely, overexpression of Runx3 enhanced tumour-specific CD8+ T cell abundance, delayed tumour growth, and prolonged survival. In addition to establishing Runx3 as a central regulator of T_RM cell differentiation, these results provide insight into the signals that promote T cell residency in non-lymphoid sites, which could be used to enhance vaccine efficacy or adoptive cell therapy treatments that target cancer.

doi: 10.1038/nature24993

A non-canonical Notch complex regulates adherens junctions and vascular barrier function p.258

doi: 10.1038/nature24998

RNA polymerase III limits longevity downstream of TORC1 p.263

doi: 10.1038/nature25007

piRNA-mediated regulation of transposon alternative splicing in the soma and germ line p.268

doi: 10.1038/nature25018

KAT2A coupled with the α-KGDH complex acts as a histone H3 succinyltransferase p.273

Histone modifications, such as the frequently occurring lysine succinylation, are central to the regulation of chromatin-based processes. However, the mechanism and functional consequences of histone succinylation are unknown. Here we show that the α-ketoglutarate dehydrogenase (α-KGDH) complex is localized in the nucleus in human cell lines and binds to lysine acetyltransferase 2A (KAT2A, also known as GCN5) in the promoter regions of genes. We show that succinyl-coenzyme A (succinyl-CoA) binds to KAT2A. The crystal structure of the catalytic domain of KAT2A in complex with succinyl-CoA at 2.3 Å resolution shows that succinyl-CoA binds to a deep cleft of KAT2A with the succinyl moiety pointing towards the end of a flexible loop 3, which adopts different structural conformations in succinyl-CoA-bound and acetyl-CoA-bound forms. Site-directed mutagenesis indicates that tyrosine 645 in this loop has an important role in the selective binding of succinyl-CoA over acetyl-CoA. KAT2A acts as a succinyltransferase and succinylates histone H3 on lysine 79, with a maximum frequency around the transcription start sites of genes. Preventing the α-KGDH complex from entering the nucleus, or expression of KAT2A(Tyr645Ala), reduces gene expression and inhibits tumour cell proliferation and tumour growth. These findings reveal an important mechanism of histone modification and demonstrate that local generation of succinyl-CoA by the nuclear α-KGDH complex coupled with the succinyltransferase activity of KAT2A is instrumental in histone succinylation, tumour cell proliferation, and tumour development.

doi: 10.1038/nature25003