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RNA–DNA hybrids and R-loop structures are widespread during transcription, replication and DNA repair. R-loops regulate gene expression, but their unfettered accumulation causes genome instability and contributes to neurodegeneration and cancer. Recent mechanistic understanding of R-loop suppression provides therapeutic opportunities to target them.
Apical–basal polarity is essential for epithelial cell form and function. Elucidating how distinct apical and basolateral compartments are established and maintained is essential to better understand the roles of apical–basal cell polarization in morphogenesis and how defects in polarity contribute to diseases such as cancer.
Heterochromatin DNA is heavily methylated yet also inaccessible. Olivier Mathieu describes the work that revealed how DNA methyltransferases access heterochromatin.
The transcription factor c-Maf is required for the specification of liver sinusoids and for the maintenance of a specialized sinusoidal network necessary for sustaining hepatocyte function.
The configuration of microtubule networks is cell type-specific and strongly correlates with cell function and behaviour. The regulation of microtubule nucleation, dynamics and distribution all contribute to the establishment and remodelling of these functionally diverse microtubule architectures.
Mechanical signalling underlies multiple, fundamental biological processes. Mechanical signals can originate from substrate physical properties or shear stresses, and from changes in the physical properties of the cell surface. The mechanisms underlying these two classes of outside-in signalling and their roles in the regulation of intracellular signalling in cell fate and development are becoming increasingly understood.
Arnold et al. document an alternative tricarboxylic acid cycle that takes place between the mitochondria and the cytosol and that can be adopted in specific cell states.
Pioneer transcription factors activate gene enhancers through their unique ability to initiate opening of inaccessible chromatin. Pioneer factors are crucial for cell fate determination in development and for cellular reprogramming, and their misexpression has major pathological consequences in cancer.
Extracellular vesicles (EVs) mediate cell–cell communication in physiology and pathology but many questions remain about the mechanisms governing their delivery to recipient cells. This Expert Recommendation article highlights areas of progress and challenges in establishing the importance of EV-mediated communication in vivo.
Topoisomerases have essential roles in transcription, DNA replication, chromatin remodelling and, as recently revealed, 3D genome organization. However, topoisomerases also generate DNA–protein crosslinks coupled with DNA breaks, which are increasingly recognized as a source of disease-causing genomic damage.
The regulatory sequences carried by transposable elements (TEs) often recruit the transcription machinery and affect host gene expression. Recent studies have revealed mechanisms by which TEs contribute to transcription regulation, including donation of enhancer and promoter sequences, modification of 3D chromatin architecture, and generation of novel regulatory non-coding RNAs and transcription factors.