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Meeting Report

Gathering by the Red Sea highlights links between environment and epigenetics pp491 - 493

Mo Li, Emiliana Borrelli, Pierre J Magistretti, Juan Carlos Izpisua Belmonte, Paolo Sassone-Corsi & Valerio Orlando


The number of conferences on epigenetics has been increasing in the past decade, underscoring the impact of the field on a variety of areas in biology and medicine. However, the mechanistic role of the epigenome in adaptation and inheritance, and how the environment may impinge on epigenetic control, are topics of growing debate. Those themes were the focus of the inaugural international King Abdullah University of Science and Technology (KAUST) Research Conference on Environmental Epigenetics in Saudi Arabia, where more than 100 participants from 19 countries enjoyed vibrant scientific discussions and a pleasant February breeze from the Red Sea.


News and Views

Promoter interactions direct chromatin folding in embryonic stem cells pp494 - 495

Swastika Sanyal, Lucia Molnarova & Juraj Gregan


The spatial organization of the genome profoundly influences how genes are regulated in normal development or dysregulated in disease. A new study of the murine HoxB locus illustrates how promoter interactions direct higher-order chromatin folding.

See also: Article by Barbieri et al.

Distinct mechanisms obviate the potentially toxic effects of inverted-repeat Alu elements on cellular RNA metabolism pp496 - 498

Reyad A Elbarbary & Lynne E Maquat


Two new studies show that RNA-binding proteins can mediate distinct and beneficial effects to cells by binding to the extensive double-stranded RNA (dsRNA) structures of inverted-repeat Alu elements (IRAlus). One study reports stress-induced export of the 110-kDa isoform of the adenosine deaminase acting on RNA 1 protein (ADAR1p110) to the cytoplasm, where it binds IRAlus so as to protect many mRNAs encoding anti-apoptotic proteins from degradation. The other study demonstrates that binding of the nuclear helicase DHX9 to IRAlus embedded within RNAs minimizes defects in RNA processing.

See also: Article by Sakurai et al.

A glimpse into chromatin remodeling pp498 - 500

Dale B Wigley & Gregory D Bowman


Chromatin remodelers are ATP-driven enzymes that can slide nucleosomes along DNA. Chen and colleagues present a tantalizing ~4-Å view of the SWI/SNF ATPase motor bound to the nucleosome, which offers novel structural clues into the remodeling process.

Frozen in action: cryo-EM structure of a GPCR–G-protein complex pp500 - 502

Mithu Baidya, Hemlata Dwivedi & Arun K Shukla


Interaction with heterotrimeric G proteins is a hallmark of G-protein-coupled receptor (GPCR) family members, and it is the key step for a diverse range of cell-signaling cascades. A recent cryo-EM structure of the human calcitonin receptor (CTR) in complex with a G-protein heterotrimer reveals novel insights into receptor–G-protein coupling.

RNA base-pairing drives phase transitions p502

Anke Sparmann




DNA N6-methyladenine in metazoans: functional epigenetic mark or bystander? pp503 - 506

Guan-Zheng Luo & Chuan He


The DNA-adenine modification 6mA has recently been identified in metazoans. This Perspective summarizes the latest discoveries and suggests potential functional roles for 6mA in metazoan genomes.



Human CTP synthase filament structure reveals the active enzyme conformation pp507 - 514

Eric M Lynch, Derrick R Hicks, Matthew Shepherd, James A Endrizzi, Allison Maker, Jesse M Hansen, Rachael M Barry, Zemer Gitai, Enoch P Baldwin & Justin M Kollman


The human enzyme CTP synthase forms polymeric filaments with increased catalytic activity, in contrast to the inactive filaments formed by bacterial CTP synthase. Cryo-EM and crystallographic analyses explain the structural bases for those different behaviors.

Active and poised promoter states drive folding of the extended HoxB locus in mouse embryonic stem cells pp515 - 524

Mariano Barbieri, Sheila Q Xie, Elena Torlai Triglia, Andrea M Chiariello, Simona Bianco, Inês de Santiago, Miguel R Branco, David Rueda, Mario Nicodemi & Ana Pombo


Homotypic interactions between active and Polycomb-repressed promoters co-occurring in the same DNA fiber, rather than CTCF occupancy, explain the 3D HoxB folding pattern.

See also: News and Views by Sanyal et al.

The myosin mesa and the basis of hypercontractility caused by hypertrophic cardiomyopathy mutations pp525 - 533

Suman Nag, Darshan V Trivedi, Saswata S Sarkar, Arjun S Adhikari, Margaret S Sunitha, Shirley Sutton, Kathleen M Ruppel & James A Spudich


A working model for β-cardiac myosin in the sequestered state and binding assays reveal interactions between the myosin head and tail that are disrupted by mutations associated with hypertrophic cardiomyopathy.

ADAR1 controls apoptosis of stressed cells by inhibiting Staufen1-mediated mRNA decay pp534 - 543

Masayuki Sakurai, Yusuke Shiromoto, Hiromitsu Ota, Chunzi Song, Andrew V Kossenkov, Jayamanna Wickramasinghe, Louise C Showe, Emmanuel Skordalakes, Hsin-Yao Tang, David W Speicher & Kazuko Nishikura


In stressed cells, the ADAR1p110 isoform is phosphorylated and translocated from the nucleus to the cytoplasm, where it protects transcripts with 3′-UTR dsRNA structures from Staufen1-mediated decay, thus suppressing cellular apoptosis.

See also: News and Views by Elbarbary & Maquat

5-Formylcytosine does not change the global structure of DNA pp544 - 552

Jack S Hardwick, Denis Ptchelkine, Afaf H El-Sagheer, Ian Tear, Daniel Singleton, Simon E V Phillips, Andrew N Lane & Tom Brown


X-ray crystallography and NMR analysis demonstrate that, contrary to previous observations, fC does not significantly alter DNA structure, thus suggesting an alternative basis for recognition of fC-DNA by epigenome-modifying enzymes.



Erratum: Molecular basis of telomere dysfunction in human genetic diseases p553

Grzegorz Sarek, Paulina Marzec, Pol Margalef & Simon J Boulton




Corrigendum: Quaternary contact in the initial interaction of CD4 with the HIV-1 envelope trimer p553

Qingbo Liu, Priyamvada Acharya, Michael A Dolan, Peng Zhang, Christina Guzzo, Jacky Lu, Alice Kwon, Deepali Gururani, Huiyi Miao, Tatsiana Bylund, Gwo-Yu Chuang, Aliaksandr Druz, Tongqing Zhou, William J Rice, Christoph Wigge, Bridget Carragher, Clinton S Potter, Peter D Kwong & Paolo Lusso