Volume 23 Issue 8, August 2021

Many endocytic uptake events depend on the ‘pinchase’ activity of dynamin. By measuring the orientation of single gold nanorods, a new study reveals that invaginated clathrin-coated endocytic pits undergo a strong rotational twist prior to or concomitant with their detachment.

Lineage-specific gene expression programs in multicellular organisms are controlled by balanced ON and OFF signals, amongst which heterochromatin regulates expression by restricting activation cues. A study now provides insights into mammalian heterochromatin organisation, function and interplay with lineage-specific transcription factors.

LKB1 is frequently mutated in lung, cervical and other types of cancers. To determine how LKB1 inactivation contributes to lung cancer progression, Pierce et al. employed a chromatin accessibility assay to reveal Sox17 as a key transcription factor downstream of LKB1, promoting lung cancer metastasis.

Cells rely on two main pathways to repair DNA lesions, homologous recombination and non-homologous end-joining, and how they decide to use one machinery over the other is not clear. A recent study identifies ASTE1 as a regulator controlling pathway choice.

Neuronal mitochondria perturbation elicits a mitochondrial unfolded protein response (UPR^mt) in peripheral tissues cell non-autonomously, dependent on the Wnt signalling pathway. A study now reveals that a Wnt-mediated increase in maternally inherited mitochondria DNA is responsible for transgenerational UPR^mt induced by neuronal mitochondria perturbation.

Studying SARS-CoV-2 in organoids. Chen et al. review the emerging roles of complex organoids in the study of SARS-CoV-2 infection, modelling of COVID-19 disease pathology and in drug, antibody and vaccine development.

Using systematic mutagenesis maps, Roberts, Ozkan et al. study how dynamic nucleosome binding of OCT4 modulates chromatin accessibility during cell fate changes and in pluripotency maintenance.

Claude-Taupin et al. show that ATG9A mediates protection against plasma membrane damage in diverse biological contexts through a mechanism involving IQGAP1 and ESCRTs.

Using gold nanorods and 3D-SPORT to track dynamin-induced fission in live cells, Cheng et al. show that endocytic vesicles undergo a rapid, large rotation before fission, which requires dynamin’s GTPase activity.

Zhang et al. report that the systemic mitochondrial unfolded protein response triggered by neuronal mitochondrial stress can be transmitted across multiple generations in Caenorhabditis elegans via a mechanism involving elevation in mitochondrial DNA levels in oocytes.

Soochit et al. report that the residence time of CTCF on chromatin is controlled by its zinc finger 8 domain and determines chromatin organization, DNA methylation and transcriptional robustness in mouse embryonic stem cells.

Zhao et al. show that ASTE1 is a downstream effector of the shieldin complex, which cleaves the 3′ overhang of DNA double-strand breaks to promote shieldin-dependent non-homologous end-joining.

McCarthy, Kaeding et al. identify H3K9me3-heterochromatin proteins that repress heterochromatic genes with implications in hepatic reprogramming and show that ERH is key to global H3K9me3 maintenance in human cells.

Pierce et al perform genome-wide CRISPR screening and identify LKB1 as a regulator of chromatin accessibility and metastatic progression in lung cancer through a mechanism of SOX17-mediated epigenetic changes.