Volume 23 Issue 4, April 2021

The conserved chromatin remodeller DECREASED IN DNA METHYLATION 1 (DDM1) has long been an enigma given its powerful but likely indirect effect in maintaining plant DNA methylation. In this issue of Nature Cell Biology, Osakabe et al. show that the direct action of DDM1 is deposition of the H2A.W histone variant to silence transposable elements.

STING is a key player in the IFN response to cytosolic DNA, and its multimerization is commonly associated with activation of the pathway. A new study now shows that STING forms ‘puzzle’-like condensates to limit the IFN response and constrain antiviral immune activation.

Endocytosis is critical for regulating plasma membrane composition and function. The mechanisms that control the assembly and dynamic rearrangement of the endocytic protein network to enable endocytic vesicle formation have remained elusive. Two endocytic initiator proteins are now shown to form liquid-like condensates to initiate endocytosis.

The transition of endothelial cells between quiescence and proliferation is essential for regulating the extent of the vasculature that supplies oxygen and nutrients to tissues. A study now shows that the FOXO1 transcription factor regulates endothelial cell proliferation by controlling levels of the metabolite 2-hydroxyglutarate.

Legube and Marnef review the association between R-loops and DNA repair. They discuss how R-loops are formed near DNA double-strand breaks (DSBs) and how R-loops affect transcription near DSBs and DSB repair processes.

Using gastruloids and human embryos, Yang et al. demonstrate that aneuploid embryos can still lead to healthy births due to elimination of aneuploid cells by apoptosis in a BMP4-dependent manner.

Weijts et al. present a model of vasculogenesis in zebrafish whereby endothelial cells form a network of struts, allowing de novo formation of large-diameter blood vessels without a vascular cord or hollowing step.

Yu et al. identify that STING bicondensates occur in virus-infected cells, thereby restricting TBK1 activation and innate immunity.

Yi et al. report that EZH2 exerts a PRC2-independent function in nucleoli, where it bridges FBL and NOP56 to facilitate rRNA methylation and subsequent IRES-dependent translation.

Here Liu et al. show that genome-wide redistribution of methyltransferase-like 3 and 14 transcriptionally promotes the senescence-associated secretory phenotype in an m⁶A-independent manner.

Phase separation promotes clathrin-mediated endocytosis; Day et al. show that Eps15 and Fcho1 rely on weak, liquid-like interactions to efficiently catalyse endocytosis.

Ponsioen et al. use a FRET‐based ERK biosensor EKAREN5 in patient‐derived organoids to show that EGFR activity amplifies signal transduction efficiency in KRAS or BRAF mutant MAPK pathways.

Osakabe et al. report that the chromatin remodeler DDM1 silences transposable elements by mediating H2A.W deposition in Arabidopsis.

Monserrat et al. report that MSL inactivation suppresses tumour maintenance via enhancing chromosomal instability (CIN). Mechanistically, H4K16ac loss upon MSL inactivation generates under-replicated DNA, leading to CIN.

Andrade et al. show that FOXO1 regulates mitochondrial metabolism to stimulate the production of the metabolite S-2HG to promote acquisition of a quiescent endothelial state.

Shi et al. profiled small non-coding RNAs (sncRNAs) through PANDORA-seq, which identified tissue-specific transfer RNA- and ribosomal RNA-derived small RNAs, as well as sncRNAs, with dynamic changes during induced pluripotent stem cell reprogramming.