Reviews & Analysis

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.

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.

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.

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.

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.

A new study shows that the SARS-CoV-2 nucleocapsid protein represses the antiviral type I interferon response through direct interaction with the signalling adaptor protein MAVS. Targeting this process might be a useful therapeutic strategy to boost immunity against COVID-19.

A form of programmed cell death, necroptosis, in intestinal epithelial cells initiates mucosal inflammation. A study now finds that prostanoid EP4 receptor signalling interferes with RIPK1–RIPK3-dependent MLKL activation, thereby inhibiting necroptosis and accelerating resolution of inflammation.

Intestinal organoids have been used to model development of the crypt–villus axis and uncover signalling pathways that govern the stem-cell niche and induce differentiation. Two studies now take advantage of intestinal organoids to measure the mechanical forces that drive morphogenesis of the crypt and fate specification of its resident cells.

Transcription-coupled repair of DNA lesions takes place across all domains of life. A transcription-elongation factor, ELOF1, highly conserved in eukaryotes, has now been shown to play a key role in this process. Importantly, these findings also include evidence of a second transcription-coupled repair pathway in mammalian cells.

COVID-19 has led to a global pandemic, but the long-term immunological effects of the infection are only partially understood. A new study now provides important new clues by describing the transcriptional and epigenetic processes behind the immune memory of both adaptive and innate immune cells in individuals who have recovered from COVID-19.

In this Perspective, Fuxreiter and Vendruscolo discuss the fundamental nature of the droplet and amyloid states of proteins, the regulatory mechanisms controlling their formation, and the cellular functions associated with these condensed states.

The vascular system, plastic and positioned in the vicinity of tissues, is an undervalued regulator of adult stem cells. Two studies now show that the vascular-like Drosophila trachea is reshaped after intestinal damage or tumour formation and that this remodelling is required for compensatory intestinal stem cell proliferation and tumour growth.

Monocytes, plasmacytoid and conventional dendritic cells are crucial for antiviral immune responses. A new study now compares severe and moderate cases of COVID-19 and links defects in viral sensing, interferon and antigen presentation pathways, associated with upregulated apoptosis and inflammatory pathways, to high COVID-19 severity.

The distribution of skin immune cells, namely Langerhans cells (LCs) and dendritic epidermal T cells (DETCs), is well-documented, but the mechanisms underlying their pattern maintenance remained obscure. A study now finds that LCs maintain their distribution patterns depending upon Rac1 and that the density of LCs and DETCs is regulated by the density of epithelial cells.

Overcoming immune resistance mechanisms in patients with cancer is critical for successful immunotherapy. A new study now identifies LIMIT as an immunogenic long non-coding RNA (lncRNA) that intrinsically regulates anti-tumour immune responses, thereby highlighting the therapeutic potential of targeting lncRNAs to improve the outcome of cancer immunotherapy.

Epigenetic barriers need to be surmounted in order to increase the efficiency of cardiac reprogramming. A new study now reports that the histone reader PHF7 enhances cardiac reprogramming via recruiting the chromatin remodelling SWI/SNF complex and key transcription factors to the cardiac super enhancers.

In this Review, Hurley and colleagues cover the most recent discoveries and the emerging molecular understanding of the mechanisms of autophagosome formation.

Chromosomal instability (CIN) is a hallmark of malignant evolution that underpins cancer progression and therapeutic evasion. There are few established experimental systems to study CIN and ultimately develop potential therapeutic options. A new study now identifies the MSL chromatin complex as a potential vulnerability against CIN in cancer cells.

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.